Carrel name: keyword-cns-cord Creating study carrel named keyword-cns-cord Initializing database file: cache/cord-001332-dp6vzgef.json key: cord-001332-dp6vzgef authors: Hosking, Martin P.; Lane, Thomas E. title: ELR(+) chemokine signaling in host defense and disease in a viral model of central nervous system disease date: 2014-06-17 journal: Front Cell Neurosci DOI: 10.3389/fncel.2014.00165 sha: doc_id: 1332 cord_uid: dp6vzgef file: cache/cord-001017-4qfhltg4.json key: cord-001017-4qfhltg4 authors: Chatterjee, Dhriti; Biswas, Kaushiki; Nag, Soma; Ramachandra, S. G.; Das Sarma, Jayasri title: Microglia Play a Major Role in Direct Viral-Induced Demyelination date: 2013-06-20 journal: Clin Dev Immunol DOI: 10.1155/2013/510396 sha: doc_id: 1017 cord_uid: 4qfhltg4 file: cache/cord-002209-xs6qigg4.json key: cord-002209-xs6qigg4 authors: Kıray, Hülya; Lindsay, Susan L.; Hosseinzadeh, Sara; Barnett, Susan C. title: The multifaceted role of astrocytes in regulating myelination date: 2016-09-17 journal: Exp Neurol DOI: 10.1016/j.expneurol.2016.03.009 sha: doc_id: 2209 cord_uid: xs6qigg4 file: cache/cord-006824-btcdjmfp.json key: cord-006824-btcdjmfp authors: nan title: Key Note and State of the Art Lectures date: 2002-09-07 journal: Ann Hematol DOI: 10.1007/s00277-002-0513-0 sha: doc_id: 6824 cord_uid: btcdjmfp file: cache/cord-002119-kl431ev6.json key: cord-002119-kl431ev6 authors: Garcia, Elisa; Aguilar-Cevallos, Jorge; Silva-Garcia, Raul; Ibarra, Antonio title: Cytokine and Growth Factor Activation In Vivo and In Vitro after Spinal Cord Injury date: 2016-06-23 journal: Mediators Inflamm DOI: 10.1155/2016/9476020 sha: doc_id: 2119 cord_uid: kl431ev6 file: cache/cord-016954-l3b6n7ej.json key: cord-016954-l3b6n7ej authors: Young, Colin R.; Welsh, C. Jane title: Animal Models of Multiple Sclerosis date: 2008 journal: Sourcebook of Models for Biomedical Research DOI: 10.1007/978-1-59745-285-4_69 sha: doc_id: 16954 cord_uid: l3b6n7ej file: cache/cord-000725-rafwlw0t.json key: cord-000725-rafwlw0t authors: Hindinger, Claudia; Bergmann, Cornelia C.; Hinton, David R.; Phares, Timothy W.; Parra, Gabriel I.; Hussain, Shabbir; Savarin, Carine; Atkinson, Roscoe D.; Stohlman, Stephen A. title: IFN-γ Signaling to Astrocytes Protects from Autoimmune Mediated Neurological Disability date: 2012-07-27 journal: PLoS One DOI: 10.1371/journal.pone.0042088 sha: doc_id: 725 cord_uid: rafwlw0t file: cache/cord-005734-14ba78cz.json key: cord-005734-14ba78cz authors: Bennett, Jami L.; Elhofy, Adam; Dal Canto, Mauro C.; Tani, Mari; Ransohoff, Richard M.; Karpus, William J. title: CCL2 transgene expression in the central nervous system directs diffuse infiltration of CD45(high)CD11b(+) monocytes and enhanced Theiler’s murine encephalomyelitis virus-induced demyelinating disease date: 2003 journal: J Neurovirol DOI: 10.1080/13550280390247551 sha: doc_id: 5734 cord_uid: 14ba78cz file: cache/cord-002757-upwe0cpj.json key: cord-002757-upwe0cpj authors: Sullivan, Kathleen E.; Bassiri, Hamid; Bousfiha, Ahmed A.; Costa-Carvalho, Beatriz T.; Freeman, Alexandra F.; Hagin, David; Lau, Yu L.; Lionakis, Michail S.; Moreira, Ileana; Pinto, Jorge A.; de Moraes-Pinto, M. Isabel; Rawat, Amit; Reda, Shereen M.; Reyes, Saul Oswaldo Lugo; Seppänen, Mikko; Tang, Mimi L. K. title: Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies date: 2017-08-07 journal: J Clin Immunol DOI: 10.1007/s10875-017-0426-2 sha: doc_id: 2757 cord_uid: upwe0cpj file: cache/cord-007603-27m9wz0i.json key: cord-007603-27m9wz0i authors: Rall, Glenn F.; Mucke, Lennart; Nerenberg, Michael; Oldstone, Michael B.A. title: A transgenic mouse model to assess the interaction of cytotoxic T lymphocytes with virally infected, class I MHC-expressing astrocytes date: 2002-11-11 journal: J Neuroimmunol DOI: 10.1016/0165-5728(94)90163-5 sha: doc_id: 7603 cord_uid: 27m9wz0i file: cache/cord-009577-29u7pdpk.json key: cord-009577-29u7pdpk authors: Gonzalez‐Scarano, F.; Tyler, Kenneth L. title: Molecular pathogenesis of neurotropic viral infections date: 2004-10-08 journal: Ann Neurol DOI: 10.1002/ana.410220502 sha: doc_id: 9577 cord_uid: 29u7pdpk file: cache/cord-005393-rhji4io9.json key: cord-005393-rhji4io9 authors: Popko, Brian; Corbin, Joshua G.; Baerwald, Kristine D.; Dupree, Jeffrey; Garcia, Annie M. title: The effects of interferon-γ on the central nervous system date: 1997 journal: Mol Neurobiol DOI: 10.1007/bf02740619 sha: doc_id: 5393 cord_uid: rhji4io9 file: cache/cord-004911-fbge8tkc.json key: cord-004911-fbge8tkc authors: Imrich, H.; Harzer, K. title: On the role of peripheral macrophages during active experimental allergic encephalomyelitis (EAE) date: 2001 journal: J Neural Transm (Vienna) DOI: 10.1007/s007020170060 sha: doc_id: 4911 cord_uid: fbge8tkc file: cache/cord-008530-yni0poh9.json key: cord-008530-yni0poh9 authors: Asensio, Valerie C.; Campbell, lain L. title: Chemokines and viral diseases of the central nervous system date: 2004-01-07 journal: Adv Virus Res DOI: 10.1016/s0065-3527(01)56006-6 sha: doc_id: 8530 cord_uid: yni0poh9 file: cache/cord-010187-ymhcfyxx.json key: cord-010187-ymhcfyxx authors: Gromeier, Matthias; Lu, Hui-Hua; Wimmer, Eckard title: Mouse neuropathogenic poliovirus strains cause damage in the central nervous system distinct from poliomyelitis date: 2005-03-25 journal: Microb Pathog DOI: 10.1016/s0882-4010(05)80002-6 sha: doc_id: 10187 cord_uid: ymhcfyxx file: cache/cord-002021-67ao8chx.json key: cord-002021-67ao8chx authors: Kim, Seong Bum; Choi, Jin Young; Uyangaa, Erdenebileg; Patil, Ajit Mahadev; Hossain, Ferdaus Mohd Altaf; Hur, Jin; Park, Sang-Youel; Lee, John-Hwa; Kim, Koanhoi; Eo, Seong Kug title: Blockage of indoleamine 2,3-dioxygenase regulates Japanese encephalitis via enhancement of type I/II IFN innate and adaptive T-cell responses date: 2016-04-18 journal: J Neuroinflammation DOI: 10.1186/s12974-016-0551-5 sha: doc_id: 2021 cord_uid: 67ao8chx file: cache/cord-010016-fs8pjy1z.json key: cord-010016-fs8pjy1z authors: WEBB, H. E.; FAZAKERLEY, J. K. title: CAN VIRAL ENVELOPE GLYCOLIPIDS PRODUCE AUTO‐IMMUNITY, WITH REFERENCE TO THE CNS AND MULTIPLE SCLEROSIS? date: 2008-05-12 journal: Neuropathol Appl Neurobiol DOI: 10.1111/j.1365-2990.1984.tb00335.x sha: doc_id: 10016 cord_uid: fs8pjy1z file: cache/cord-011533-im78xwl8.json key: cord-011533-im78xwl8 authors: Gloude, Nicholas J.; Dandoy, Christopher E.; Davies, Stella M.; Myers, Kasiani C.; Jordan, Michael B.; Marsh, Rebecca A.; Kumar, Ashish; Bleesing, Jack; Teusink-Cross, Ashley; Jodele, Sonata title: Thinking Beyond HLH: Clinical Features of Patients with Concurrent Presentation of Hemophagocytic Lymphohistiocytosis and Thrombotic Microangiopathy date: 2020-05-23 journal: J Clin Immunol DOI: 10.1007/s10875-020-00789-4 sha: doc_id: 11533 cord_uid: im78xwl8 file: cache/cord-008523-avkgldnp.json key: cord-008523-avkgldnp authors: Perlman, Stanley; Wu, Gregory F. title: Selection of and evasion from cytotoxic T cell responses in the central nervous system date: 2004-01-07 journal: Adv Virus Res DOI: 10.1016/s0065-3527(01)56029-7 sha: doc_id: 8523 cord_uid: avkgldnp file: cache/cord-003738-el0wyu74.json key: cord-003738-el0wyu74 authors: Zhang, Qingxiu; Zhu, Wen; Xu, Fei; Dai, Xuejiao; Shi, Ligen; Cai, Wei; Mu, Hongfeng; Hitchens, T. Kevin; Foley, Lesley M.; Liu, Xiangrong; Yu, Fang; Chen, Jie; Shi, Yejie; Leak, Rehana K.; Gao, Yanqin; Chen, Jun; Hu, Xiaoming title: The interleukin-4/PPARγ signaling axis promotes oligodendrocyte differentiation and remyelination after brain injury date: 2019-06-21 journal: PLoS Biol DOI: 10.1371/journal.pbio.3000330 sha: doc_id: 3738 cord_uid: el0wyu74 file: cache/cord-008586-5jinvuyn.json key: cord-008586-5jinvuyn authors: Loihl, Angela K.; Murphy, Sean title: Chapter 18 Expression of nitric oxide synthase-2 in glia associated with CNS pathology date: 2008-04-10 journal: Prog Brain Res DOI: 10.1016/s0079-6123(08)63213-6 sha: doc_id: 8586 cord_uid: 5jinvuyn file: cache/cord-017144-k7fqneup.json key: cord-017144-k7fqneup authors: Oleszak, Emilia L.; Kuzmak, Jacek; Varadhachary, Arun; Katsetos, Christos D. title: Nitric Oxide in TMEV date: 2005 journal: Experimental Models of Multiple Sclerosis DOI: 10.1007/0-387-25518-4_35 sha: doc_id: 17144 cord_uid: k7fqneup file: cache/cord-018034-gx5c9mk8.json key: cord-018034-gx5c9mk8 authors: nan title: Cell and Tissue Reactions date: 2006 journal: Forensic Neuropathology and Associated Neurology DOI: 10.1007/3-540-28995-x_4 sha: doc_id: 18034 cord_uid: gx5c9mk8 file: cache/cord-018042-qt7055fw.json key: cord-018042-qt7055fw authors: Müller, Marcus; Campbell, Iain L. title: Chemokine Actions in the CNS: Insights from Transgenic Mice date: 2008 journal: Central Nervous System Diseases and Inflammation DOI: 10.1007/978-0-387-73894-9_10 sha: doc_id: 18042 cord_uid: qt7055fw file: cache/cord-007170-svsfu7fj.json key: cord-007170-svsfu7fj authors: Richt, J. A.; VandeWoude, S.; Zink, M. C.; Clements, J. E.; Herzog, S.; Stitz, L.; Rott, R.; Narayan, O. title: Infection with Borna Disease Virus: Molecular and Immunobiological Characterization of the Agent date: 1992-06-17 journal: Clin Infect Dis DOI: 10.1093/clinids/14.6.1240 sha: doc_id: 7170 cord_uid: svsfu7fj file: cache/cord-001396-rpnuauwz.json key: cord-001396-rpnuauwz authors: Blanc, Caroline A; Rosen, Hugh; Lane, Thomas E title: FTY720 (fingolimod) modulates the severity of viral-induced encephalomyelitis and demyelination date: 2014-08-20 journal: J Neuroinflammation DOI: 10.1186/s12974-014-0138-y sha: doc_id: 1396 cord_uid: rpnuauwz file: cache/cord-005146-o3roa7br.json key: cord-005146-o3roa7br authors: Sasaki, Makoto; Ide, Chizuka title: Demyelination and remyelination in the dorsal funiculus of the rat spinal cord after heat injury date: 1989 journal: J Neurocytol DOI: 10.1007/bf01206664 sha: doc_id: 5146 cord_uid: o3roa7br file: cache/cord-017917-7aeh6quc.json key: cord-017917-7aeh6quc authors: Marten, Norman W.; Zhou, Jiehao title: The Role of Metalloproteinases in Corona Virus Infection date: 2005 journal: Experimental Models of Multiple Sclerosis DOI: 10.1007/0-387-25518-4_48 sha: doc_id: 17917 cord_uid: 7aeh6quc file: cache/cord-021452-9rukc80y.json key: cord-021452-9rukc80y authors: Bergman, Robert L. title: Miscellaneous Spinal Cord Diseases date: 2009-05-15 journal: Consultations in Feline Internal Medicine DOI: 10.1016/b0-72-160423-4/50054-8 sha: doc_id: 21452 cord_uid: 9rukc80y file: cache/cord-015684-q10sx1dm.json key: cord-015684-q10sx1dm authors: Cacabelos, Ramón title: Pharmacogenomic Biomarkers in Neuropsychiatry: The Path to Personalized Medicine in Mental Disorders date: 2009 journal: The Handbook of Neuropsychiatric Biomarkers, Endophenotypes and Genes DOI: 10.1007/978-90-481-2298-1_1 sha: doc_id: 15684 cord_uid: q10sx1dm file: cache/cord-003199-03c9rx3o.json key: cord-003199-03c9rx3o authors: Singh, Manmeet; Khan, Reas S.; Dine, Kimberly; Das Sarma, Jayasri; Shindler, Kenneth S. title: Intracranial Inoculation Is More Potent Than Intranasal Inoculation for Inducing Optic Neuritis in the Mouse Hepatitis Virus-Induced Model of Multiple Sclerosis date: 2018-09-04 journal: Front Cell Infect Microbiol DOI: 10.3389/fcimb.2018.00311 sha: doc_id: 3199 cord_uid: 03c9rx3o file: cache/cord-017499-51yy7y9n.json key: cord-017499-51yy7y9n authors: Freye, Enno; Levy, Joseph Victor title: Mechanism of Action of Opioids and Clinical Effects date: 2008 journal: Opioids in Medicine DOI: 10.1007/978-1-4020-5947-6_2 sha: doc_id: 17499 cord_uid: 51yy7y9n file: cache/cord-021069-v9f9874x.json key: cord-021069-v9f9874x authors: Morrison, Lynda A.; Fields, Bernard N. title: Viral pathogenesis and central nervous system infection date: 2004-11-23 journal: nan DOI: 10.1016/1044-5765(91)90002-6 sha: doc_id: 21069 cord_uid: v9f9874x file: cache/cord-022163-7klzsrpu.json key: cord-022163-7klzsrpu authors: Broder, Christopher C.; Wong, Kum Thong title: Henipaviruses date: 2016-09-09 journal: Neurotropic Viral Infections DOI: 10.1007/978-3-319-33133-1_3 sha: doc_id: 22163 cord_uid: 7klzsrpu file: cache/cord-020770-wpub7krf.json key: cord-020770-wpub7krf authors: Benmamar-Badel, Anouk; Owens, Trevor; Wlodarczyk, Agnieszka title: Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies date: 2020-04-03 journal: Front Immunol DOI: 10.3389/fimmu.2020.00430 sha: doc_id: 20770 cord_uid: wpub7krf file: cache/cord-022395-rk31pwoa.json key: cord-022395-rk31pwoa authors: Schuller-Levis, Georgia; Kozlowski, Piotr B.; Kascsak, Richard J. title: Central Nervous System: Viral Infection and Immune-Mediated Inflammation date: 2012-12-02 journal: Xenobiotics and Inflammation DOI: 10.1016/b978-0-12-628930-5.50019-9 sha: doc_id: 22395 cord_uid: rk31pwoa file: cache/cord-028963-u4iupl1s.json key: cord-028963-u4iupl1s authors: Lane, Michael; Yadav, Vijayshree title: Multiple Sclerosis date: 2020-07-10 journal: Textbook of Natural Medicine DOI: 10.1016/b978-0-323-43044-9.00199-0 sha: doc_id: 28963 cord_uid: u4iupl1s file: cache/cord-252389-xrdbmosj.json key: cord-252389-xrdbmosj authors: Kumar, Mukesh; Thakur, Ajit Kumar title: Neurological manifestations and comorbidity associated with COVID-19: an overview date: 2020-10-14 journal: Neurol Sci DOI: 10.1007/s10072-020-04823-6 sha: doc_id: 252389 cord_uid: xrdbmosj file: cache/cord-017958-18nnwoav.json key: cord-017958-18nnwoav authors: Chan, Andrew; Gold, Ralf title: Apoptotic Cell Death in Experimental Autoimmune Encephalomyelitis: Apoptosis of effector cells as a safe mechanism in the termination of an autoimmune inflammatory attack date: 2005 journal: Experimental Models of Multiple Sclerosis DOI: 10.1007/0-387-25518-4_24 sha: doc_id: 17958 cord_uid: 18nnwoav file: cache/cord-267166-ecmayzr6.json key: cord-267166-ecmayzr6 authors: Savarin, Carine; Dutta, Ranjan; Bergmann, Cornelia C. title: Distinct Gene Profiles of Bone Marrow-Derived Macrophages and Microglia During Neurotropic Coronavirus-Induced Demyelination date: 2018-06-11 journal: Front Immunol DOI: 10.3389/fimmu.2018.01325 sha: doc_id: 267166 cord_uid: ecmayzr6 file: cache/cord-022756-kdgo4rqb.json key: cord-022756-kdgo4rqb authors: nan title: Hematopoietic Tumors date: 2012-11-28 journal: Withrow and MacEwen's Small Animal Clinical Oncology DOI: 10.1016/b978-1-4377-2362-5.00032-3 sha: doc_id: 22756 cord_uid: kdgo4rqb file: cache/cord-017954-vobslprh.json key: cord-017954-vobslprh authors: Croxford, J. Ludovic; Miyake, Sachiko title: Animal Models for the Study of Neuroimmunological Disease date: 2016-03-26 journal: Neuroimmunological Diseases DOI: 10.1007/978-4-431-55594-0_3 sha: doc_id: 17954 cord_uid: vobslprh file: cache/cord-253201-r6vsa0pw.json key: cord-253201-r6vsa0pw authors: Nazari, S.; Azari Jafari, A.; Mirmoeeni, S.; Sadeghian, S.; Heidari, M. E.; Asarzadegan, F.; Puormand, S. M.; Alikhani, K.; Ebadi, H.; Fathi, D.; Dalvand, S. title: Central Nervous System Manifestations in COVID-19 Patients: A Systematic Review and Meta-analysis date: 2020-07-22 journal: nan DOI: 10.1101/2020.07.21.20158691 sha: doc_id: 253201 cord_uid: r6vsa0pw file: cache/cord-104265-kcygxo7h.json key: cord-104265-kcygxo7h authors: Brabb, Thea; von Dassow, Peter; Ordonez, Nadia; Schnabel, Bryan; Duke, Blythe; Goverman, Joan title: In Situ Tolerance within the Central Nervous System as a Mechanism for Preventing Autoimmunity date: 2000-09-18 journal: J Exp Med DOI: nan sha: doc_id: 104265 cord_uid: kcygxo7h file: cache/cord-022594-fx044gcd.json key: cord-022594-fx044gcd authors: Pirko, Istvan; Noseworthy, John H. title: Demyelinating Disorders of the Central Nervous System date: 2009-05-18 journal: Textbook of Clinical Neurology DOI: 10.1016/b978-141603618-0.10048-7 sha: doc_id: 22594 cord_uid: fx044gcd file: cache/cord-021500-sy6lnt7b.json key: cord-021500-sy6lnt7b authors: Jean Harry, G.; Toews, Arrel D. title: Myelination, Dysmyelination, and Demyelination date: 2007-05-09 journal: Handbook of Developmental Neurotoxicology DOI: 10.1016/b978-012648860-9.50007-8 sha: doc_id: 21500 cord_uid: sy6lnt7b file: cache/cord-252569-9rv1p3qh.json key: cord-252569-9rv1p3qh authors: Zanella, M.-C.; Lenggenhager, L.; Schrenzel, J.; Cordey, S.; Kaiser, L. title: High-throughput sequencing for the aetiologic identification of viral encephalitis, meningoencephalitis, and meningitis. A narrative review and clinical appraisal date: 2019-01-11 journal: Clin Microbiol Infect DOI: 10.1016/j.cmi.2018.12.022 sha: doc_id: 252569 cord_uid: 9rv1p3qh file: cache/cord-264794-bgygebgx.json key: cord-264794-bgygebgx authors: Lundgren, A.-L. title: Feline non-suppurative meningoencephalomyelitis. A clinical and pathological study date: 1992-11-30 journal: Journal of Comparative Pathology DOI: 10.1016/0021-9975(92)90015-m sha: doc_id: 264794 cord_uid: bgygebgx file: cache/cord-274315-08mk8a86.json key: cord-274315-08mk8a86 authors: DiSano, Krista D.; Stohlman, Stephen A.; Bergmann, Cornelia C. title: An optimized method for enumerating CNS derived memory B cells during viral-induced inflammation date: 2017-06-15 journal: Journal of Neuroscience Methods DOI: 10.1016/j.jneumeth.2017.05.011 sha: doc_id: 274315 cord_uid: 08mk8a86 file: cache/cord-253797-a9lmfaho.json key: cord-253797-a9lmfaho authors: Eddleston, M.; Mucke, L. title: Molecular profile of reactive astrocytes—Implications for their role in neurologic disease date: 1993-05-31 journal: Neuroscience DOI: 10.1016/0306-4522(93)90380-x sha: doc_id: 253797 cord_uid: a9lmfaho file: cache/cord-297325-fbilhauu.json key: cord-297325-fbilhauu authors: Savarin, Carine; Bergmann, Cornelia C.; Gaignage, Melanie; Stohlman, Stephen A. title: Self-reactive CD4(+) T cells activated during viral-induced demyelination do not prevent clinical recovery date: 2015-11-11 journal: J Neuroinflammation DOI: 10.1186/s12974-015-0426-1 sha: doc_id: 297325 cord_uid: fbilhauu file: cache/cord-270084-xs0pbcip.json key: cord-270084-xs0pbcip authors: Stohlman, Stephen A.; Sussman, Mark A.; Matsushima, Glenn K.; Shubin, Richard A.; Erlich, Stephanie S. title: Delayed-type hypersensitivity response in the central nervous system during JHM virus infection requires viral specificity for protection date: 1988-09-30 journal: Journal of Neuroimmunology DOI: 10.1016/0165-5728(88)90007-0 sha: doc_id: 270084 cord_uid: xs0pbcip file: cache/cord-270458-7imgvale.json key: cord-270458-7imgvale authors: Franchini, Massimo; Farrugia, Albert; Velati, Claudio; Zanetti, Alessandro; Romanò, Luisa; Grazzini, Giuliano; Lopez, Nadia; Pati, Ilaria; Marano, Giuseppe; Pupella, Simonetta; Liumbruno, Giancarlo Maria title: The impact of the SARS‐CoV‐2 outbreak on the safety and availability of blood transfusions in Italy date: 2020-04-13 journal: Vox Sang DOI: 10.1111/vox.12928 sha: doc_id: 270458 cord_uid: 7imgvale file: cache/cord-266078-h53zpjab.json key: cord-266078-h53zpjab authors: McGuckin Wuertz, Kathryn; Treuting, Piper M.; Hemann, Emily A.; Esser-Nobis, Katharina; Snyder, Annelise G.; Graham, Jessica B.; Daniels, Brian P.; Wilkins, Courtney; Snyder, Jessica M.; Voss, Kathleen M.; Oberst, Andrew; Lund, Jennifer; Gale, Michael title: STING is required for host defense against neuropathological West Nile virus infection date: 2019-08-15 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1007899 sha: doc_id: 266078 cord_uid: h53zpjab file: cache/cord-021772-5v4gor2v.json key: cord-021772-5v4gor2v authors: Levine, Gwendolyn J.; Cook, Jennifer R. title: Cerebrospinal Fluid and Central Nervous System Cytology date: 2019-05-31 journal: Cowell and Tyler's Diagnostic Cytology and Hematology of the Dog and Cat DOI: 10.1016/b978-0-323-53314-0.00014-6 sha: doc_id: 21772 cord_uid: 5v4gor2v file: cache/cord-023143-fcno330z.json key: cord-023143-fcno330z authors: nan title: Molecular aspects of viral immunity date: 2004-02-19 journal: J Cell Biochem DOI: 10.1002/jcb.240591009 sha: doc_id: 23143 cord_uid: fcno330z file: cache/cord-022659-chwk2bs4.json key: cord-022659-chwk2bs4 authors: nan title: Abstracts: Poster session date: 2004-10-08 journal: Ann Neurol DOI: 10.1002/ana.410320224 sha: doc_id: 22659 cord_uid: chwk2bs4 file: cache/cord-276587-ynionj5r.json key: cord-276587-ynionj5r authors: Hwang, Mihyun; Bergmann, Cornelia C. title: Alpha/Beta Interferon (IFN-α/β) Signaling in Astrocytes Mediates Protection against Viral Encephalomyelitis and Regulates IFN-γ-Dependent Responses date: 2018-04-27 journal: J Virol DOI: 10.1128/jvi.01901-17 sha: doc_id: 276587 cord_uid: ynionj5r file: cache/cord-270780-3g381rzr.json key: cord-270780-3g381rzr authors: Bradshaw, J. M.; Pearson, G. R.; Gruffydd-Jones, T. J. title: A Retrospective Study of 286 Cases of Neurological Disorders of the Cat date: 2004-10-31 journal: Journal of Comparative Pathology DOI: 10.1016/j.jcpa.2004.01.010 sha: doc_id: 270780 cord_uid: 3g381rzr file: cache/cord-276533-cxyndepl.json key: cord-276533-cxyndepl authors: McFarland, Henry F.; Dhib-Jalbut, Suhayl title: Multiple sclerosis: Possible immunological mechanisms date: 1989-01-31 journal: Clinical Immunology and Immunopathology DOI: 10.1016/0090-1229(89)90116-5 sha: doc_id: 276533 cord_uid: cxyndepl file: cache/cord-268341-103xf3dw.json key: cord-268341-103xf3dw authors: Parra, Beatriz; Hinton, David R.; Lin, Mark T.; Cua, Daniel J.; Stohlman, Stephen A. title: Kinetics of Cytokine mRNA Expression in the Central Nervous System Following Lethal and Nonlethal Coronavirus-Induced Acute Encephalomyelitis date: 1997-07-07 journal: Virology DOI: 10.1006/viro.1997.8613 sha: doc_id: 268341 cord_uid: 103xf3dw file: cache/cord-271176-wdc4p4bc.json key: cord-271176-wdc4p4bc authors: González-Scarano, Francisco; Rima, Bert title: Infectious etiology in multiple sclerosis: the debate continues date: 1999-12-01 journal: Trends Microbiol DOI: 10.1016/s0966-842x(99)01634-0 sha: doc_id: 271176 cord_uid: wdc4p4bc file: cache/cord-266441-sd117tzs.json key: cord-266441-sd117tzs authors: Almutrafi, Amna; Bashawry, Yara; AlShakweer, Wafaa; Al-Harbi, Musa; Altwairgi, Abdullah; Al-Dandan, Sadeq title: The Epidemiology of Primary Central Nervous System Tumors at the National Neurologic Institute in Saudi Arabia: A Ten-Year Single-Institution Study date: 2020-02-15 journal: J Cancer Epidemiol DOI: 10.1155/2020/1429615 sha: doc_id: 266441 cord_uid: sd117tzs file: cache/cord-262281-56tbrl8a.json key: cord-262281-56tbrl8a authors: Hawkes, C. H.; Del Tredici, K.; Braak, H. title: Parkinson's disease: a dual‐hit hypothesis date: 2007-10-24 journal: Neuropathol Appl Neurobiol DOI: 10.1111/j.1365-2990.2007.00874.x sha: doc_id: 262281 cord_uid: 56tbrl8a file: cache/cord-271396-bol1zpji.json key: cord-271396-bol1zpji authors: Manglani, Monica; McGavern, Dorian B title: New advances in CNS immunity against viral infection date: 2018-02-28 journal: Current Opinion in Virology DOI: 10.1016/j.coviro.2017.12.003 sha: doc_id: 271396 cord_uid: bol1zpji file: cache/cord-030371-wp6xmaqe.json key: cord-030371-wp6xmaqe authors: Kubota, Kazuo; Ogawa, Mikako; Ji, Bin; Watabe, Tadashi; Zhang, Ming-Rong; Suzuki, Hiromi; Sawada, Makoto; Nishi, Kodai; Kudo, Takashi title: Basic Science of PET Imaging for Inflammatory Diseases date: 2019-12-21 journal: PET/CT for Inflammatory Diseases DOI: 10.1007/978-981-15-0810-3_1 sha: doc_id: 30371 cord_uid: wp6xmaqe file: cache/cord-015352-2d02eq3y.json key: cord-015352-2d02eq3y authors: nan title: ESPR 2017 date: 2017-04-26 journal: Pediatr Radiol DOI: 10.1007/s00247-017-3820-2 sha: doc_id: 15352 cord_uid: 2d02eq3y file: cache/cord-271011-5stsx5je.json key: cord-271011-5stsx5je authors: Singh, M.; Foster, D.J.; Child, G.; Lamb, W.A. title: Inflammatory cerebrospinal fluid analysis in cats: clinical diagnosis and outcome date: 2005-03-09 journal: J Feline Med Surg DOI: 10.1016/j.jfms.2004.07.001 sha: doc_id: 271011 cord_uid: 5stsx5je file: cache/cord-278684-txlvla0j.json key: cord-278684-txlvla0j authors: Gonzalez–Dunia, Daniel; Sauder, Christian; de la Torre, Juan Carlos title: Borna Disease Virus and the Brain date: 1998-01-30 journal: Brain Res Bull DOI: 10.1016/s0361-9230(97)00276-1 sha: doc_id: 278684 cord_uid: txlvla0j file: cache/cord-268835-catuja6c.json key: cord-268835-catuja6c authors: Libbey, Jane E.; McCoy, Lori L.; Fujinami, Robert S. title: Molecular Mimicry in Multiple Sclerosis date: 2007-12-31 journal: International Review of Neurobiology DOI: 10.1016/s0074-7742(07)79006-2 sha: doc_id: 268835 cord_uid: catuja6c file: cache/cord-302796-zi3p2k1b.json key: cord-302796-zi3p2k1b authors: Cardona, Astrid E.; Li, Meizhang; Liu, Liping; Savarin, Carine; Ransohoff, Richard M. title: Chemokines in and out of the central nervous system: much more than chemotaxis and inflammation date: 2008-05-08 journal: Journal of Leukocyte Biology DOI: 10.1189/jlb.1107763 sha: doc_id: 302796 cord_uid: zi3p2k1b file: cache/cord-259347-3acsko74.json key: cord-259347-3acsko74 authors: Cheng, Qi; Yang, Yue; Gao, Jianqun title: Infectivity of human coronavirus in the brain date: 2020-05-28 journal: EBioMedicine DOI: 10.1016/j.ebiom.2020.102799 sha: doc_id: 259347 cord_uid: 3acsko74 file: cache/cord-283850-kt8n6pg2.json key: cord-283850-kt8n6pg2 authors: Steardo, Luca; Steardo, Luca; Verkhratsky, Alexei title: Psychiatric face of COVID-19 date: 2020-07-30 journal: Transl Psychiatry DOI: 10.1038/s41398-020-00949-5 sha: doc_id: 283850 cord_uid: kt8n6pg2 file: cache/cord-303741-1ou0cy5k.json key: cord-303741-1ou0cy5k authors: Stafstrom, Carl E.; Jantzie, Lauren L. title: COVID-19: Neurological Considerations in Neonates and Children date: 2020-09-10 journal: Children (Basel) DOI: 10.3390/children7090133 sha: doc_id: 303741 cord_uid: 1ou0cy5k file: cache/cord-280987-uhxk5b1b.json key: cord-280987-uhxk5b1b authors: Turtle, L.; Solomon, T. title: Encephalitis, Viral date: 2014-05-01 journal: Encyclopedia of the Neurological Sciences DOI: 10.1016/b978-0-12-385157-4.00375-4 sha: doc_id: 280987 cord_uid: uhxk5b1b file: cache/cord-262786-otxpc46a.json key: cord-262786-otxpc46a authors: Mohammadi, Soheil; Moosaie, Fatemeh; Aarabi, Mohammad Hadi title: Understanding the Immunologic Characteristics of Neurologic Manifestations of SARS-CoV-2 and Potential Immunological Mechanisms date: 2020-09-01 journal: Mol Neurobiol DOI: 10.1007/s12035-020-02094-y sha: doc_id: 262786 cord_uid: otxpc46a file: cache/cord-285493-eg2ltip6.json key: cord-285493-eg2ltip6 authors: Schwab, S.; Herden, C.; Seeliger, F.; Papaioannou, N.; Psalla, D.; Polizopulou, Z.; Baumgärtner, W. title: Non-suppurative Meningoencephalitis of Unknown Origin in Cats and Dogs: an Immunohistochemical Study date: 2007-02-01 journal: J Comp Pathol DOI: 10.1016/j.jcpa.2006.11.006 sha: doc_id: 285493 cord_uid: eg2ltip6 file: cache/cord-297448-aiorjsyh.json key: cord-297448-aiorjsyh authors: Atkinson, Jeffrey R.; Hwang, Mihyun; Reyes-Rodriguez, Angel; Bergmann, Cornelia C. title: Dynamics of Virus-Specific Memory B Cells and Plasmablasts following Viral Infection of the Central Nervous System date: 2019-01-04 journal: J Virol DOI: 10.1128/jvi.00875-18 sha: doc_id: 297448 cord_uid: aiorjsyh file: cache/cord-272981-8gahvdt0.json key: cord-272981-8gahvdt0 authors: Wege, Helmut; Watanabe, Rihito; ter Meulen, Volker title: Relapsing subacute demyelinating encephalomyelitis in rats during the course of coronavirus JHM infection date: 1984-08-31 journal: Journal of Neuroimmunology DOI: 10.1016/0165-5728(84)90022-5 sha: doc_id: 272981 cord_uid: 8gahvdt0 file: cache/cord-269861-r07osd0w.json key: cord-269861-r07osd0w authors: Kim, Jin Hyoung; Patil, Ajit Mahadev; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Hossain, Ferdaus Mohd Altaf; Park, Sang-Youel; Lee, John Hwa; Eo, Seong Kug title: CCR5 ameliorates Japanese encephalitis via dictating the equilibrium of regulatory CD4(+)Foxp3(+) T and IL-17(+)CD4(+) Th17 cells date: 2016-07-20 journal: J Neuroinflammation DOI: 10.1186/s12974-016-0656-x sha: doc_id: 269861 cord_uid: r07osd0w file: cache/cord-298847-szezd2vb.json key: cord-298847-szezd2vb authors: Jacomy, Hélène; Talbot, Pierre J title: Vacuolating encephalitis in mice infected by human coronavirus OC43 date: 2003-10-10 journal: Virology DOI: 10.1016/s0042-6822(03)00323-4 sha: doc_id: 298847 cord_uid: szezd2vb file: cache/cord-299051-5r2s8z1a.json key: cord-299051-5r2s8z1a authors: Tsuhako, Maria Heloisa; Augusto, Ohara; Linares, Edlaine; Chadi, Gerson; Giorgio, Selma; Pereira, Carlos A. title: Tempol ameliorates murine viral encephalomyelitis by preserving the blood–brain barrier, reducing viral load, and lessening inflammation date: 2010-03-01 journal: Free Radic Biol Med DOI: 10.1016/j.freeradbiomed.2009.12.013 sha: doc_id: 299051 cord_uid: 5r2s8z1a file: cache/cord-277679-sc9hugxr.json key: cord-277679-sc9hugxr authors: Khateb, Mohamed; Bosak, Noam; Muqary, Maryam title: Coronaviruses and Central Nervous System Manifestations date: 2020-06-23 journal: Front Neurol DOI: 10.3389/fneur.2020.00715 sha: doc_id: 277679 cord_uid: sc9hugxr file: cache/cord-288111-0ufc54kw.json key: cord-288111-0ufc54kw authors: ter MEULEN, VOLKER title: Autoimmune Reactions Against Myelin Basic Protein Induced by Corona and Measles Viruses date: 2006-12-17 journal: Ann N Y Acad Sci DOI: 10.1111/j.1749-6632.1988.tb27062.x sha: doc_id: 288111 cord_uid: 0ufc54kw file: cache/cord-294812-nnlzwaf1.json key: cord-294812-nnlzwaf1 authors: Desforges, Marc; Le Coupanec, Alain; Brison, Élodie; Meessen-Pinard, Mathieu; Talbot, Pierre J. title: Neuroinvasive and Neurotropic Human Respiratory Coronaviruses: Potential Neurovirulent Agents in Humans date: 2014-03-12 journal: Infectious Diseases and Nanomedicine I DOI: 10.1007/978-81-322-1777-0_6 sha: doc_id: 294812 cord_uid: nnlzwaf1 file: cache/cord-292255-zafnq8gl.json key: cord-292255-zafnq8gl authors: Trojano, M.; Avolio, C. title: Chapter 8 Environmental Factors and Their Regulation of Immunity in Multiple Sclerosis date: 2016-12-31 journal: Translational Neuroimmunology in Multiple Sclerosis DOI: 10.1016/b978-0-12-801914-6.00008-8 sha: doc_id: 292255 cord_uid: zafnq8gl file: cache/cord-295041-5vpawtef.json key: cord-295041-5vpawtef authors: Jakhmola, Shweta; Indari, Omkar; Chatterjee, Sayantani; Jha, Hem Chandra title: SARS-CoV-2, an Underestimated Pathogen of the Nervous System date: 2020-09-28 journal: SN Compr Clin Med DOI: 10.1007/s42399-020-00522-7 sha: doc_id: 295041 cord_uid: 5vpawtef file: cache/cord-284038-93s3ffoy.json key: cord-284038-93s3ffoy authors: Keyhanian, Kiandokht; Umeton, Raffaella Pizzolato; Mohit, Babak; Davoudi, Vahid; Hajighasemi, Fatemeh; Ghasemi, Mehdi title: SARS-CoV-2 and nervous system: From pathogenesis to clinical manifestation date: 2020-11-07 journal: J Neuroimmunol DOI: 10.1016/j.jneuroim.2020.577436 sha: doc_id: 284038 cord_uid: 93s3ffoy file: cache/cord-275795-ee7qyw5h.json key: cord-275795-ee7qyw5h authors: Monette, Anne; Mouland, Andrew J. title: T Lymphocytes as Measurable Targets of Protection and Vaccination Against Viral Disorders date: 2018-10-24 journal: Int Rev Cell Mol Biol DOI: 10.1016/bs.ircmb.2018.07.006 sha: doc_id: 275795 cord_uid: ee7qyw5h file: cache/cord-311908-sgdq6j6x.json key: cord-311908-sgdq6j6x authors: Atkins, G. J.; McQuaid, S.; Morris‐Downes, M. M.; Galbraith, S. E.; Amor, S.; Cosby, S. L.; Sheahan, B. J. title: Transient virus infection and multiple sclerosis date: 2000-09-28 journal: Rev Med Virol DOI: 10.1002/1099-1654(200009/10)10:5<291::aid-rmv278>3.0.co;2-u sha: doc_id: 311908 cord_uid: sgdq6j6x file: cache/cord-299949-kmn53e2z.json key: cord-299949-kmn53e2z authors: Schultz, Kimberly L.W.; Griffin, Diane E. title: Immune Responses to Viruses in the CNS date: 2016-05-09 journal: Encyclopedia of Immunobiology DOI: 10.1016/b978-0-12-374279-7.14022-6 sha: doc_id: 299949 cord_uid: kmn53e2z file: cache/cord-317651-lsca8vt2.json key: cord-317651-lsca8vt2 authors: Yong, V. Wee; Power, Christopher; Forsyth, Peter; Edwards, Dylan R. title: Metalloproteinases in biology and pathology of the nervous system date: 2001 journal: Nat Rev Neurosci DOI: 10.1038/35081571 sha: doc_id: 317651 cord_uid: lsca8vt2 file: cache/cord-315656-asvf4roo.json key: cord-315656-asvf4roo authors: Wu, Junjiao; Tang, Yu title: Revisiting the Immune Balance Theory: A Neurological Insight Into the Epidemic of COVID-19 and Its Alike date: 2020-10-15 journal: Front Neurol DOI: 10.3389/fneur.2020.566680 sha: doc_id: 315656 cord_uid: asvf4roo file: cache/cord-311845-wnk7itha.json key: cord-311845-wnk7itha authors: Lubetzki, Catherine; Stankoff, Bruno title: Demyelination in multiple sclerosis date: 2014-02-05 journal: Handb Clin Neurol DOI: 10.1016/b978-0-444-52001-2.00004-2 sha: doc_id: 311845 cord_uid: wnk7itha file: cache/cord-290566-tmsocyfc.json key: cord-290566-tmsocyfc authors: Chitnis, Tanuja title: The Role of CD4 T Cells in the Pathogenesis of Multiple Sclerosis date: 2007-05-25 journal: Int Rev Neurobiol DOI: 10.1016/s0074-7742(07)79003-7 sha: doc_id: 290566 cord_uid: tmsocyfc file: cache/cord-299967-90aknp7c.json key: cord-299967-90aknp7c authors: Terry, Rachael L; Getts, Daniel R; Deffrasnes, Celine; van Vreden, Caryn; Campbell, Iain L; King, Nicholas JC title: Inflammatory monocytes and the pathogenesis of viral encephalitis date: 2012-12-17 journal: J Neuroinflammation DOI: 10.1186/1742-2094-9-270 sha: doc_id: 299967 cord_uid: 90aknp7c file: cache/cord-312064-hza70mur.json key: cord-312064-hza70mur authors: Borrow, P; Welsh, C J; Tonks, P; Dean, D; Blakemore, W F; Nash, A A title: Investigation of the role of delayed-type-hypersensitivity responses to myelin in the pathogenesis of Theiler's virus-induced demyelinating disease. date: 1998-04-17 journal: Immunology DOI: nan sha: doc_id: 312064 cord_uid: hza70mur file: cache/cord-349285-zmp7sw5q.json key: cord-349285-zmp7sw5q authors: Koh, Kyung‐Nam; Im, Ho Joon; Chung, Nak‐Gyun; Cho, Bin; Kang, Hyoung Jin; Shin, Hee Young; Lyu, Chuhl Joo; Yoo, Keon Hee; Koo, Hong Hoe; Kim, Hee‐Jin; Baek, Hee Jo; Kook, Hoon; Yoon, Hoi Soo; Lim, Young Tak; Kim, Heung Sik; Ryu, Kyung Ha; Seo, Jong Jin title: Clinical features, genetics, and outcome of pediatric patients with hemophagocytic lymphohistiocytosis in Korea: report of a nationwide survey from Korea Histiocytosis Working Party date: 2014-07-03 journal: Eur J Haematol DOI: 10.1111/ejh.12399 sha: doc_id: 349285 cord_uid: zmp7sw5q file: cache/cord-309109-c5hajb6k.json key: cord-309109-c5hajb6k authors: Matthews, A. E.; Weiss, S. R.; Paterson, Y. title: Murine hepatitis virus—A model for virus-induced CNS demyelination date: 2002 journal: J Neurovirol DOI: 10.1080/13550280290049534 sha: doc_id: 309109 cord_uid: c5hajb6k file: cache/cord-320909-p93gxjm2.json key: cord-320909-p93gxjm2 authors: Natoli, S.; Oliveira, V.; Calabresi, P.; Maia, L. F.; Pisani, A. title: Does SARS‐Cov‐2 invade the brain? Translational lessons from animal models date: 2020-05-22 journal: Eur J Neurol DOI: 10.1111/ene.14277 sha: doc_id: 320909 cord_uid: p93gxjm2 file: cache/cord-345254-glm2dxhh.json key: cord-345254-glm2dxhh authors: Hwang, Mihyun; Phares, Timothy W; Hinton, David R; Stohlman, Stephen A; Bergmann, Cornelia C; Min, Booki title: Distinct CD4 T-cell effects on primary versus recall CD8 T-cell responses during viral encephalomyelitis date: 2015-02-13 journal: Immunology DOI: 10.1111/imm.12378 sha: doc_id: 345254 cord_uid: glm2dxhh file: cache/cord-311847-2czqs84q.json key: cord-311847-2czqs84q authors: Pennisi, Manuela; Lanza, Giuseppe; Falzone, Luca; Fisicaro, Francesco; Ferri, Raffaele; Bella, Rita title: SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms date: 2020-07-31 journal: Int J Mol Sci DOI: 10.3390/ijms21155475 sha: doc_id: 311847 cord_uid: 2czqs84q file: cache/cord-328763-hcbs20a0.json key: cord-328763-hcbs20a0 authors: Ifergan, Igal; Miller, Stephen D. title: Potential for Targeting Myeloid Cells in Controlling CNS Inflammation date: 2020-10-06 journal: Front Immunol DOI: 10.3389/fimmu.2020.571897 sha: doc_id: 328763 cord_uid: hcbs20a0 file: cache/cord-338235-vz2d2x18.json key: cord-338235-vz2d2x18 authors: Pinschewer, Daniel D.; Schedensack, Mariann; Bergthaler, Andreas; Horvath, Edit; Brück, Wolfgang; Löhning, Max; Merkler, Doron title: T cells can mediate viral clearance from ependyma but not from brain parenchyma in a major histocompatibility class I- and perforin-independent manner date: 2010-03-30 journal: Brain DOI: 10.1093/brain/awq028 sha: doc_id: 338235 cord_uid: vz2d2x18 file: cache/cord-325624-6anybxnk.json key: cord-325624-6anybxnk authors: Ireland, Derek D. C.; Stohlman, Stephen A.; Hinton, David R.; Kapil, Parul; Silverman, Robert H.; Atkinson, Roscoe A.; Bergmann, Cornelia C. title: RNase L Mediated Protection from Virus Induced Demyelination date: 2009-10-02 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1000602 sha: doc_id: 325624 cord_uid: 6anybxnk file: cache/cord-329527-0rlotyz3.json key: cord-329527-0rlotyz3 authors: Bohmwald, Karen; Gálvez, Nicolás M. S.; Ríos, Mariana; Kalergis, Alexis M. title: Neurologic Alterations Due to Respiratory Virus Infections date: 2018-10-26 journal: Front Cell Neurosci DOI: 10.3389/fncel.2018.00386 sha: doc_id: 329527 cord_uid: 0rlotyz3 file: cache/cord-324530-tac1unnp.json key: cord-324530-tac1unnp authors: André, Nicole M; Cossic, Brieuc; Davies, Emma; Miller, Andrew D; Whittaker, Gary R title: Distinct mutation in the feline coronavirus spike protein cleavage activation site in a cat with feline infectious peritonitis-associated meningoencephalomyelitis date: 2019-06-26 journal: JFMS Open Rep DOI: 10.1177/2055116919856103 sha: doc_id: 324530 cord_uid: tac1unnp file: cache/cord-304084-ervaxqph.json key: cord-304084-ervaxqph authors: Chang, Luan-Yin; Hsiung, Chao A; Lu, Chun-Yi; Lin, Tzou-Yien; Huang, Fu-Yuan; Lai, Yu-Han; Chiang, Yu-Ping; Chiang, Bor-Luen; Lee, Chin-Yun; Huang, Li-Min title: Status of Cellular Rather Than Humoral Immunity is Correlated with Clinical Outcome of Enterovirus 71 date: 2006 journal: Pediatr Res DOI: 10.1203/01.pdr.0000238247.86041.19 sha: doc_id: 304084 cord_uid: ervaxqph file: cache/cord-349135-it5ahzj3.json key: cord-349135-it5ahzj3 authors: Lane, T. E.; Hardison, J. L.; Walsh, K. B. title: Functional Diversity of Chemokines and Chemokine Receptors in Response to Viral Infection of the Central Nervous System date: 2006 journal: Chemokines and Viral Infection DOI: 10.1007/978-3-540-33397-5_1 sha: doc_id: 349135 cord_uid: it5ahzj3 file: cache/cord-316227-dgyxbgvg.json key: cord-316227-dgyxbgvg authors: Geginat, Jens; Paroni, Moira; Pagani, Massimiliano; Galimberti, Daniela; De Francesco, Raffaele; Scarpini, Elio; Abrignani, Sergio title: The Enigmatic Role of Viruses in Multiple Sclerosis: Molecular Mimicry or Disturbed Immune Surveillance? date: 2017-05-23 journal: Trends Immunol DOI: 10.1016/j.it.2017.04.006 sha: doc_id: 316227 cord_uid: dgyxbgvg file: cache/cord-320617-ucm7wx8b.json key: cord-320617-ucm7wx8b authors: B’Krong, Nguyen Thi Thuy Chinh; Minh, Ngo Ngoc Quang; Qui, Phan Tu; Chau, Tran Thi Hong; Nghia, Ho Dang Trung; Do, Lien Anh Ha; Nhung, Nguyen Ngoc; Van Vinh Chau, Nguyen; Thwaites, Guy; Van Tan, Le; van Doorn, H. Rogier; Thanh, Tran Tan title: Enterovirus serotypes in patients with central nervous system and respiratory infections in Viet Nam 1997–2010 date: 2018-04-12 journal: Virol J DOI: 10.1186/s12985-018-0980-0 sha: doc_id: 320617 cord_uid: ucm7wx8b file: cache/cord-329750-purunxce.json key: cord-329750-purunxce authors: Waldman, Amy; O'Connor, Erin; Tennekoon, Gihan title: Childhood multiple sclerosis: A review date: 2006-06-28 journal: Ment Retard Dev Disabil Res Rev DOI: 10.1002/mrdd.20105 sha: doc_id: 329750 cord_uid: purunxce file: cache/cord-346339-y7z1sa8y.json key: cord-346339-y7z1sa8y authors: Baumgärtner, Wolfgang; Löscher, Wolfgang title: Re-emergence of neuroinfectiology date: 2016-01-11 journal: Acta Neuropathol DOI: 10.1007/s00401-016-1535-3 sha: doc_id: 346339 cord_uid: y7z1sa8y file: cache/cord-334499-fz7vrnb1.json key: cord-334499-fz7vrnb1 authors: Templeton, Steven P.; Perlman, Stanley title: Pathogenesis of acute and chronic central nervous system infection with variants of mouse hepatitis virus, strain JHM date: 2007-06-01 journal: Immunol Res DOI: 10.1007/s12026-007-0079-y sha: doc_id: 334499 cord_uid: fz7vrnb1 file: cache/cord-324619-y7gilopu.json key: cord-324619-y7gilopu authors: Alam, S.B.; Willows, Steven; Kulka, Marianna; Sandhu, Jagdeep K. title: Severe acute respiratory syndrome coronavirus‐2 may be an underappreciated pathogen of the central nervous system date: 2020-07-15 journal: Eur J Neurol DOI: 10.1111/ene.14442 sha: doc_id: 324619 cord_uid: y7gilopu file: cache/cord-334577-wb6zhovi.json key: cord-334577-wb6zhovi authors: Mangale, Vrushali; Syage, Amber R.; Ekiz, H. Atakan; Skinner, Dominic D.; Cheng, Yuting; Stone, Colleen L.; Brown, R. Marshall; O'Connell, Ryan M.; Green, Kim N.; Lane, Thomas E. title: Microglia influence host defense, disease, and repair following murine coronavirus infection of the central nervous system date: 2020-05-25 journal: Glia DOI: 10.1002/glia.23844 sha: doc_id: 334577 cord_uid: wb6zhovi file: cache/cord-333186-gxs74wit.json key: cord-333186-gxs74wit authors: Ashhurst, Thomas Myles; Vreden, Caryn van; Niewold, Paula; King, Nicholas Jonathan Cole title: The plasticity of inflammatory monocyte responses to the inflamed central nervous system date: 2014-10-31 journal: Cellular Immunology DOI: 10.1016/j.cellimm.2014.07.002 sha: doc_id: 333186 cord_uid: gxs74wit file: cache/cord-351398-ftkrd1tj.json key: cord-351398-ftkrd1tj authors: Stohlman, Stephen A.; Hinton, David R. title: Viral Induced Demyelination date: 2006-04-05 journal: Brain Pathol DOI: 10.1111/j.1750-3639.2001.tb00384.x sha: doc_id: 351398 cord_uid: ftkrd1tj file: cache/cord-337365-hugenn14.json key: cord-337365-hugenn14 authors: Chen, Zhuangzhuang; Zhong, Di; Li, Guozhong title: The role of microglia in viral encephalitis: a review date: 2019-04-09 journal: J Neuroinflammation DOI: 10.1186/s12974-019-1443-2 sha: doc_id: 337365 cord_uid: hugenn14 file: cache/cord-330553-sukrjl22.json key: cord-330553-sukrjl22 authors: Stonedahl, Sarah; Clarke, Penny; Tyler, Kenneth L. title: The Role of Microglia during West Nile Virus Infection of the Central Nervous System date: 2020-08-28 journal: Vaccines (Basel) DOI: 10.3390/vaccines8030485 sha: doc_id: 330553 cord_uid: sukrjl22 file: cache/cord-353298-vr5hnzp8.json key: cord-353298-vr5hnzp8 authors: nan title: In vitro analysis of the oligodendrocyte lineage in mice during demyelination and remyelination date: 1990-09-01 journal: J Cell Biol DOI: nan sha: doc_id: 353298 cord_uid: vr5hnzp8 file: cache/cord-322728-10m3xscs.json key: cord-322728-10m3xscs authors: Severance, Emily G.; Yolken, Robert H. title: Chapter 29 Role of Immune and Autoimmune Dysfunction in Schizophrenia date: 2016-12-31 journal: Handbook of Behavioral Neuroscience DOI: 10.1016/b978-0-12-800981-9.00029-8 sha: doc_id: 322728 cord_uid: 10m3xscs file: cache/cord-331268-kzy33hdb.json key: cord-331268-kzy33hdb authors: Lynch, Sharon G.; Rose, John W. title: Multiple sclerosis date: 1996-01-31 journal: Disease-a-Month DOI: 10.1016/s0011-5029(96)90012-7 sha: doc_id: 331268 cord_uid: kzy33hdb file: cache/cord-345339-kyboibtq.json key: cord-345339-kyboibtq authors: Steiner, Israel; Nisipianu, Puiu; Wirguin, Itzhak title: Infection and the etiology and pathogenesis of multiple sclerosis date: 2001 journal: Curr Neurol Neurosci Rep DOI: 10.1007/s11910-001-0030-x sha: doc_id: 345339 cord_uid: kyboibtq file: cache/cord-348746-yaf61cmx.json key: cord-348746-yaf61cmx authors: Foley, Janet E.; Leutenegger, Christian title: A Review of Coronavirus Infection in the Central Nervous System of Cats and Mice date: 2008-06-28 journal: J Vet Intern Med DOI: 10.1111/j.1939-1676.2001.tb01572.x sha: doc_id: 348746 cord_uid: yaf61cmx file: cache/cord-342204-9tgxijvn.json key: cord-342204-9tgxijvn authors: Nuzzo, Domenico; Picone, Pasquale title: Potential neurological effects of severe COVID-19 infection date: 2020-07-03 journal: Neurosci Res DOI: 10.1016/j.neures.2020.06.009 sha: doc_id: 342204 cord_uid: 9tgxijvn file: cache/cord-355413-ls2nud43.json key: cord-355413-ls2nud43 authors: Shi, Fu-Dong; Ransohoff, Richard M. title: Nature killer cells in the central nervous system date: 2010-01-29 journal: Natural Killer Cells DOI: 10.1016/b978-0-12-370454-2.00028-4 sha: doc_id: 355413 cord_uid: ls2nud43 file: cache/cord-353242-9vy8k6du.json key: cord-353242-9vy8k6du authors: Dhaiban, Sarah; Al-Ani, Mena; Elemam, Noha Mousaad; Maghazachi, Azzam A title: Targeting Chemokines and Chemokine Receptors in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis date: 2020-09-29 journal: J Inflamm Res DOI: 10.2147/jir.s270872 sha: doc_id: 353242 cord_uid: 9vy8k6du file: cache/cord-340008-2efzyki4.json key: cord-340008-2efzyki4 authors: Haddadi, Kaveh; Asadian, Leila title: Coronavirus Disease 2019: Latest Data on Neuroinvasive Potential date: 2020-09-17 journal: Iran J Med Sci DOI: 10.30476/ijms.2020.85980.1561 sha: doc_id: 340008 cord_uid: 2efzyki4 file: cache/cord-353812-4oxbczqe.json key: cord-353812-4oxbczqe authors: Zoghi, Anahita; Ramezani, Mahtab; Roozbeh, Mehrdad; Darzam, Ilad Alavi; Sahraian, Mohammad Ali title: A case of possible atypical demyelinating event of the central nervous system following COVID-19 date: 2020-06-24 journal: Mult Scler Relat Disord DOI: 10.1016/j.msard.2020.102324 sha: doc_id: 353812 cord_uid: 4oxbczqe file: cache/cord-332109-ont0tqpn.json key: cord-332109-ont0tqpn authors: Wei, Yufeng; Shah, Rameen title: Substance Use Disorder in the COVID-19 Pandemic: A Systematic Review of Vulnerabilities and Complications date: 2020-07-18 journal: Pharmaceuticals (Basel) DOI: 10.3390/ph13070155 sha: doc_id: 332109 cord_uid: ont0tqpn file: cache/cord-308201-lavcsqov.json key: cord-308201-lavcsqov authors: Desforges, Marc; Le Coupanec, Alain; Dubeau, Philippe; Bourgouin, Andréanne; Lajoie, Louise; Dubé, Mathieu; Talbot, Pierre J. title: Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System? date: 2019-12-20 journal: Viruses DOI: 10.3390/v12010014 sha: doc_id: 308201 cord_uid: lavcsqov file: cache/cord-026031-hnf5vayd.json key: cord-026031-hnf5vayd authors: Ford, Richard B.; Mazzaferro, Elisa M. title: Emergency Care date: 2009-05-21 journal: Kirk and Bistner's Handbook of Veterinary Procedures and Emergency Treatment DOI: 10.1016/b0-72-160138-3/50002-3 sha: doc_id: 26031 cord_uid: hnf5vayd file: cache/cord-023026-2r84ndzv.json key: cord-023026-2r84ndzv authors: nan title: Posters date: 2013-06-14 journal: Glia DOI: 10.1002/glia.22530 sha: doc_id: 23026 cord_uid: 2r84ndzv file: cache/cord-257167-rz4r5sj7.json key: cord-257167-rz4r5sj7 authors: nan title: Abstracts for the 29th Annual Meeting of the Japan Neuroscience Society (Neuroscience2006) date: 2006-12-31 journal: Neuroscience Research DOI: 10.1016/j.neures.2006.04.004 sha: doc_id: 257167 cord_uid: rz4r5sj7 file: cache/cord-009997-oecpqf1j.json key: cord-009997-oecpqf1j authors: nan title: 2018 ASPHO ABSTRACTS date: 2018-03-31 journal: Pediatr Blood Cancer DOI: 10.1002/pbc.27057 sha: doc_id: 9997 cord_uid: oecpqf1j Reading metadata file and updating bibliogrpahics === updating bibliographic database Building study carrel named keyword-cns-cord parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 40786 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 39141 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 39996 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 40904 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 40257 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 40419 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 41202 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 41286 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 42161 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-001332-dp6vzgef author: Hosking, Martin P. title: ELR(+) chemokine signaling in host defense and disease in a viral model of central nervous system disease date: 2014-06-17 pages: extension: .txt txt: ./txt/cord-001332-dp6vzgef.txt cache: ./cache/cord-001332-dp6vzgef.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001332-dp6vzgef.txt' parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 42902 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 43516 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45779 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 41167 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 43650 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45812 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 37682 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45857 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 44027 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45838 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 43922 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 44659 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-007603-27m9wz0i author: Rall, Glenn F. title: A transgenic mouse model to assess the interaction of cytotoxic T lymphocytes with virally infected, class I MHC-expressing astrocytes date: 2002-11-11 pages: extension: .txt txt: ./txt/cord-007603-27m9wz0i.txt cache: ./cache/cord-007603-27m9wz0i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-007603-27m9wz0i.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 41488 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 44012 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 42025 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 46005 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 41183 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 46881 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 44049 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 44824 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45931 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 48138 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 47146 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 46521 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 47048 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45316 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 47139 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 39661 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 46533 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 47943 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 48257 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 47964 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 47353 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 48278 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 48217 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-010016-fs8pjy1z author: WEBB, H. E. title: CAN VIRAL ENVELOPE GLYCOLIPIDS PRODUCE AUTO‐IMMUNITY, WITH REFERENCE TO THE CNS AND MULTIPLE SCLEROSIS? date: 2008-05-12 pages: extension: .txt txt: ./txt/cord-010016-fs8pjy1z.txt cache: ./cache/cord-010016-fs8pjy1z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-010016-fs8pjy1z.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49304 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 48821 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49400 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 48764 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 44841 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 41478 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-000725-rafwlw0t author: Hindinger, Claudia title: IFN-γ Signaling to Astrocytes Protects from Autoimmune Mediated Neurological Disability date: 2012-07-27 pages: extension: .txt txt: ./txt/cord-000725-rafwlw0t.txt cache: ./cache/cord-000725-rafwlw0t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000725-rafwlw0t.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 48777 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-009577-29u7pdpk author: Gonzalez‐Scarano, F. title: Molecular pathogenesis of neurotropic viral infections date: 2004-10-08 pages: extension: .txt txt: ./txt/cord-009577-29u7pdpk.txt cache: ./cache/cord-009577-29u7pdpk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-009577-29u7pdpk.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 48331 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49043 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49691 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49885 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-017917-7aeh6quc author: Marten, Norman W. title: The Role of Metalloproteinases in Corona Virus Infection date: 2005 pages: extension: .txt txt: ./txt/cord-017917-7aeh6quc.txt cache: ./cache/cord-017917-7aeh6quc.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-017917-7aeh6quc.txt' === file2bib.sh === id: cord-001017-4qfhltg4 author: Chatterjee, Dhriti title: Microglia Play a Major Role in Direct Viral-Induced Demyelination date: 2013-06-20 pages: extension: .txt txt: ./txt/cord-001017-4qfhltg4.txt cache: ./cache/cord-001017-4qfhltg4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001017-4qfhltg4.txt' === file2bib.sh === id: cord-270458-7imgvale author: Franchini, Massimo title: The impact of the SARS‐CoV‐2 outbreak on the safety and availability of blood transfusions in Italy date: 2020-04-13 pages: extension: .txt txt: ./txt/cord-270458-7imgvale.txt cache: ./cache/cord-270458-7imgvale.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-270458-7imgvale.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 46095 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 43875 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-018042-qt7055fw author: Müller, Marcus title: Chemokine Actions in the CNS: Insights from Transgenic Mice date: 2008 pages: extension: .txt txt: ./txt/cord-018042-qt7055fw.txt cache: ./cache/cord-018042-qt7055fw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-018042-qt7055fw.txt' === file2bib.sh === id: cord-010187-ymhcfyxx author: Gromeier, Matthias title: Mouse neuropathogenic poliovirus strains cause damage in the central nervous system distinct from poliomyelitis date: 2005-03-25 pages: extension: .txt txt: ./txt/cord-010187-ymhcfyxx.txt cache: ./cache/cord-010187-ymhcfyxx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-010187-ymhcfyxx.txt' === file2bib.sh === id: cord-005734-14ba78cz author: Bennett, Jami L. title: CCL2 transgene expression in the central nervous system directs diffuse infiltration of CD45(high)CD11b(+) monocytes and enhanced Theiler’s murine encephalomyelitis virus-induced demyelinating disease date: 2003 pages: extension: .txt txt: ./txt/cord-005734-14ba78cz.txt cache: ./cache/cord-005734-14ba78cz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-005734-14ba78cz.txt' === file2bib.sh === id: cord-004911-fbge8tkc author: Imrich, H. title: On the role of peripheral macrophages during active experimental allergic encephalomyelitis (EAE) date: 2001 pages: extension: .txt txt: ./txt/cord-004911-fbge8tkc.txt cache: ./cache/cord-004911-fbge8tkc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-004911-fbge8tkc.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 51500 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 52824 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 53433 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50149 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50099 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-006824-btcdjmfp author: nan title: Key Note and State of the Art Lectures date: 2002-09-07 pages: extension: .txt txt: ./txt/cord-006824-btcdjmfp.txt cache: ./cache/cord-006824-btcdjmfp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-006824-btcdjmfp.txt' === file2bib.sh === id: cord-005393-rhji4io9 author: Popko, Brian title: The effects of interferon-γ on the central nervous system date: 1997 pages: extension: .txt txt: ./txt/cord-005393-rhji4io9.txt cache: ./cache/cord-005393-rhji4io9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-005393-rhji4io9.txt' === file2bib.sh === id: cord-011533-im78xwl8 author: Gloude, Nicholas J. title: Thinking Beyond HLH: Clinical Features of Patients with Concurrent Presentation of Hemophagocytic Lymphohistiocytosis and Thrombotic Microangiopathy date: 2020-05-23 pages: extension: .txt txt: ./txt/cord-011533-im78xwl8.txt cache: ./cache/cord-011533-im78xwl8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-011533-im78xwl8.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 53409 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 51421 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 52284 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-002209-xs6qigg4 author: Kıray, Hülya title: The multifaceted role of astrocytes in regulating myelination date: 2016-09-17 pages: extension: .txt txt: ./txt/cord-002209-xs6qigg4.txt cache: ./cache/cord-002209-xs6qigg4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-002209-xs6qigg4.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 52743 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-016954-l3b6n7ej author: Young, Colin R. title: Animal Models of Multiple Sclerosis date: 2008 pages: extension: .txt txt: ./txt/cord-016954-l3b6n7ej.txt cache: ./cache/cord-016954-l3b6n7ej.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-016954-l3b6n7ej.txt' === file2bib.sh === id: cord-266441-sd117tzs author: Almutrafi, Amna title: The Epidemiology of Primary Central Nervous System Tumors at the National Neurologic Institute in Saudi Arabia: A Ten-Year Single-Institution Study date: 2020-02-15 pages: extension: .txt txt: ./txt/cord-266441-sd117tzs.txt cache: ./cache/cord-266441-sd117tzs.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-266441-sd117tzs.txt' === file2bib.sh === id: cord-280987-uhxk5b1b author: Turtle, L. title: Encephalitis, Viral date: 2014-05-01 pages: extension: .txt txt: ./txt/cord-280987-uhxk5b1b.txt cache: ./cache/cord-280987-uhxk5b1b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-280987-uhxk5b1b.txt' === file2bib.sh === id: cord-272981-8gahvdt0 author: Wege, Helmut title: Relapsing subacute demyelinating encephalomyelitis in rats during the course of coronavirus JHM infection date: 1984-08-31 pages: extension: .txt txt: ./txt/cord-272981-8gahvdt0.txt cache: ./cache/cord-272981-8gahvdt0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-272981-8gahvdt0.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 43853 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 53894 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-264794-bgygebgx author: Lundgren, A.-L. title: Feline non-suppurative meningoencephalomyelitis. A clinical and pathological study date: 1992-11-30 pages: extension: .txt txt: ./txt/cord-264794-bgygebgx.txt cache: ./cache/cord-264794-bgygebgx.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-264794-bgygebgx.txt' === file2bib.sh === id: cord-008523-avkgldnp author: Perlman, Stanley title: Selection of and evasion from cytotoxic T cell responses in the central nervous system date: 2004-01-07 pages: extension: .txt txt: ./txt/cord-008523-avkgldnp.txt cache: ./cache/cord-008523-avkgldnp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-008523-avkgldnp.txt' === file2bib.sh === id: cord-349285-zmp7sw5q author: Koh, Kyung‐Nam title: Clinical features, genetics, and outcome of pediatric patients with hemophagocytic lymphohistiocytosis in Korea: report of a nationwide survey from Korea Histiocytosis Working Party date: 2014-07-03 pages: extension: .txt txt: ./txt/cord-349285-zmp7sw5q.txt cache: ./cache/cord-349285-zmp7sw5q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-349285-zmp7sw5q.txt' === file2bib.sh === id: cord-104265-kcygxo7h author: Brabb, Thea title: In Situ Tolerance within the Central Nervous System as a Mechanism for Preventing Autoimmunity date: 2000-09-18 pages: extension: .txt txt: ./txt/cord-104265-kcygxo7h.txt cache: ./cache/cord-104265-kcygxo7h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-104265-kcygxo7h.txt' === file2bib.sh === id: cord-346339-y7z1sa8y author: Baumgärtner, Wolfgang title: Re-emergence of neuroinfectiology date: 2016-01-11 pages: extension: .txt txt: ./txt/cord-346339-y7z1sa8y.txt cache: ./cache/cord-346339-y7z1sa8y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-346339-y7z1sa8y.txt' === file2bib.sh === id: cord-324530-tac1unnp author: André, Nicole M title: Distinct mutation in the feline coronavirus spike protein cleavage activation site in a cat with feline infectious peritonitis-associated meningoencephalomyelitis date: 2019-06-26 pages: extension: .txt txt: ./txt/cord-324530-tac1unnp.txt cache: ./cache/cord-324530-tac1unnp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-324530-tac1unnp.txt' === file2bib.sh === id: cord-271011-5stsx5je author: Singh, M. title: Inflammatory cerebrospinal fluid analysis in cats: clinical diagnosis and outcome date: 2005-03-09 pages: extension: .txt txt: ./txt/cord-271011-5stsx5je.txt cache: ./cache/cord-271011-5stsx5je.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-271011-5stsx5je.txt' === file2bib.sh === id: cord-267166-ecmayzr6 author: Savarin, Carine title: Distinct Gene Profiles of Bone Marrow-Derived Macrophages and Microglia During Neurotropic Coronavirus-Induced Demyelination date: 2018-06-11 pages: extension: .txt txt: ./txt/cord-267166-ecmayzr6.txt cache: ./cache/cord-267166-ecmayzr6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-267166-ecmayzr6.txt' === file2bib.sh === id: cord-002021-67ao8chx author: Kim, Seong Bum title: Blockage of indoleamine 2,3-dioxygenase regulates Japanese encephalitis via enhancement of type I/II IFN innate and adaptive T-cell responses date: 2016-04-18 pages: extension: .txt txt: ./txt/cord-002021-67ao8chx.txt cache: ./cache/cord-002021-67ao8chx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002021-67ao8chx.txt' === file2bib.sh === id: cord-342204-9tgxijvn author: Nuzzo, Domenico title: Potential neurological effects of severe COVID-19 infection date: 2020-07-03 pages: extension: .txt txt: ./txt/cord-342204-9tgxijvn.txt cache: ./cache/cord-342204-9tgxijvn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342204-9tgxijvn.txt' === file2bib.sh === id: cord-299051-5r2s8z1a author: Tsuhako, Maria Heloisa title: Tempol ameliorates murine viral encephalomyelitis by preserving the blood–brain barrier, reducing viral load, and lessening inflammation date: 2010-03-01 pages: extension: .txt txt: ./txt/cord-299051-5r2s8z1a.txt cache: ./cache/cord-299051-5r2s8z1a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-299051-5r2s8z1a.txt' === file2bib.sh === id: cord-353812-4oxbczqe author: Zoghi, Anahita title: A case of possible atypical demyelinating event of the central nervous system following COVID-19 date: 2020-06-24 pages: extension: .txt txt: ./txt/cord-353812-4oxbczqe.txt cache: ./cache/cord-353812-4oxbczqe.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-353812-4oxbczqe.txt' === file2bib.sh === id: cord-002119-kl431ev6 author: Garcia, Elisa title: Cytokine and Growth Factor Activation In Vivo and In Vitro after Spinal Cord Injury date: 2016-06-23 pages: extension: .txt txt: ./txt/cord-002119-kl431ev6.txt cache: ./cache/cord-002119-kl431ev6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002119-kl431ev6.txt' === file2bib.sh === id: cord-299967-90aknp7c author: Terry, Rachael L title: Inflammatory monocytes and the pathogenesis of viral encephalitis date: 2012-12-17 pages: extension: .txt txt: ./txt/cord-299967-90aknp7c.txt cache: ./cache/cord-299967-90aknp7c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-299967-90aknp7c.txt' === file2bib.sh === id: cord-320617-ucm7wx8b author: B’Krong, Nguyen Thi Thuy Chinh title: Enterovirus serotypes in patients with central nervous system and respiratory infections in Viet Nam 1997–2010 date: 2018-04-12 pages: extension: .txt txt: ./txt/cord-320617-ucm7wx8b.txt cache: ./cache/cord-320617-ucm7wx8b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-320617-ucm7wx8b.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-304084-ervaxqph author: Chang, Luan-Yin title: Status of Cellular Rather Than Humoral Immunity is Correlated with Clinical Outcome of Enterovirus 71 date: 2006 pages: extension: .txt txt: ./txt/cord-304084-ervaxqph.txt cache: ./cache/cord-304084-ervaxqph.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-304084-ervaxqph.txt' === file2bib.sh === id: cord-022395-rk31pwoa author: Schuller-Levis, Georgia title: Central Nervous System: Viral Infection and Immune-Mediated Inflammation date: 2012-12-02 pages: extension: .txt txt: ./txt/cord-022395-rk31pwoa.txt cache: ./cache/cord-022395-rk31pwoa.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-022395-rk31pwoa.txt' === file2bib.sh === id: cord-309109-c5hajb6k author: Matthews, A. E. title: Murine hepatitis virus—A model for virus-induced CNS demyelination date: 2002 pages: extension: .txt txt: ./txt/cord-309109-c5hajb6k.txt cache: ./cache/cord-309109-c5hajb6k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-309109-c5hajb6k.txt' === file2bib.sh === id: cord-338235-vz2d2x18 author: Pinschewer, Daniel D. title: T cells can mediate viral clearance from ependyma but not from brain parenchyma in a major histocompatibility class I- and perforin-independent manner date: 2010-03-30 pages: extension: .txt txt: ./txt/cord-338235-vz2d2x18.txt cache: ./cache/cord-338235-vz2d2x18.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-338235-vz2d2x18.txt' === file2bib.sh === id: cord-311845-wnk7itha author: Lubetzki, Catherine title: Demyelination in multiple sclerosis date: 2014-02-05 pages: extension: .txt txt: ./txt/cord-311845-wnk7itha.txt cache: ./cache/cord-311845-wnk7itha.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-311845-wnk7itha.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-348746-yaf61cmx author: Foley, Janet E. title: A Review of Coronavirus Infection in the Central Nervous System of Cats and Mice date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-348746-yaf61cmx.txt cache: ./cache/cord-348746-yaf61cmx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-348746-yaf61cmx.txt' === file2bib.sh === id: cord-324619-y7gilopu author: Alam, S.B. title: Severe acute respiratory syndrome coronavirus‐2 may be an underappreciated pathogen of the central nervous system date: 2020-07-15 pages: extension: .txt txt: ./txt/cord-324619-y7gilopu.txt cache: ./cache/cord-324619-y7gilopu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-324619-y7gilopu.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-330553-sukrjl22 author: Stonedahl, Sarah title: The Role of Microglia during West Nile Virus Infection of the Central Nervous System date: 2020-08-28 pages: extension: .txt txt: ./txt/cord-330553-sukrjl22.txt cache: ./cache/cord-330553-sukrjl22.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-330553-sukrjl22.txt' === file2bib.sh === id: cord-334577-wb6zhovi author: Mangale, Vrushali title: Microglia influence host defense, disease, and repair following murine coronavirus infection of the central nervous system date: 2020-05-25 pages: extension: .txt txt: ./txt/cord-334577-wb6zhovi.txt cache: ./cache/cord-334577-wb6zhovi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-334577-wb6zhovi.txt' === file2bib.sh === id: cord-297448-aiorjsyh author: Atkinson, Jeffrey R. title: Dynamics of Virus-Specific Memory B Cells and Plasmablasts following Viral Infection of the Central Nervous System date: 2019-01-04 pages: extension: .txt txt: ./txt/cord-297448-aiorjsyh.txt cache: ./cache/cord-297448-aiorjsyh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-297448-aiorjsyh.txt' === file2bib.sh === id: cord-334499-fz7vrnb1 author: Templeton, Steven P. title: Pathogenesis of acute and chronic central nervous system infection with variants of mouse hepatitis virus, strain JHM date: 2007-06-01 pages: extension: .txt txt: ./txt/cord-334499-fz7vrnb1.txt cache: ./cache/cord-334499-fz7vrnb1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-334499-fz7vrnb1.txt' === file2bib.sh === id: cord-345254-glm2dxhh author: Hwang, Mihyun title: Distinct CD4 T-cell effects on primary versus recall CD8 T-cell responses during viral encephalomyelitis date: 2015-02-13 pages: extension: .txt txt: ./txt/cord-345254-glm2dxhh.txt cache: ./cache/cord-345254-glm2dxhh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-345254-glm2dxhh.txt' === file2bib.sh === id: cord-355413-ls2nud43 author: Shi, Fu-Dong title: Nature killer cells in the central nervous system date: 2010-01-29 pages: extension: .txt txt: ./txt/cord-355413-ls2nud43.txt cache: ./cache/cord-355413-ls2nud43.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-355413-ls2nud43.txt' === file2bib.sh === id: cord-353298-vr5hnzp8 author: nan title: In vitro analysis of the oligodendrocyte lineage in mice during demyelination and remyelination date: 1990-09-01 pages: extension: .txt txt: ./txt/cord-353298-vr5hnzp8.txt cache: ./cache/cord-353298-vr5hnzp8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-353298-vr5hnzp8.txt' === file2bib.sh === id: cord-269861-r07osd0w author: Kim, Jin Hyoung title: CCR5 ameliorates Japanese encephalitis via dictating the equilibrium of regulatory CD4(+)Foxp3(+) T and IL-17(+)CD4(+) Th17 cells date: 2016-07-20 pages: extension: .txt txt: ./txt/cord-269861-r07osd0w.txt cache: ./cache/cord-269861-r07osd0w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-269861-r07osd0w.txt' === file2bib.sh === id: cord-325624-6anybxnk author: Ireland, Derek D. C. title: RNase L Mediated Protection from Virus Induced Demyelination date: 2009-10-02 pages: extension: .txt txt: ./txt/cord-325624-6anybxnk.txt cache: ./cache/cord-325624-6anybxnk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-325624-6anybxnk.txt' === file2bib.sh === id: cord-351398-ftkrd1tj author: Stohlman, Stephen A. title: Viral Induced Demyelination date: 2006-04-05 pages: extension: .txt txt: ./txt/cord-351398-ftkrd1tj.txt cache: ./cache/cord-351398-ftkrd1tj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-351398-ftkrd1tj.txt' === file2bib.sh === id: cord-329750-purunxce author: Waldman, Amy title: Childhood multiple sclerosis: A review date: 2006-06-28 pages: extension: .txt txt: ./txt/cord-329750-purunxce.txt cache: ./cache/cord-329750-purunxce.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-329750-purunxce.txt' === file2bib.sh === id: cord-333186-gxs74wit author: Ashhurst, Thomas Myles title: The plasticity of inflammatory monocyte responses to the inflamed central nervous system date: 2014-10-31 pages: extension: .txt txt: ./txt/cord-333186-gxs74wit.txt cache: ./cache/cord-333186-gxs74wit.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-333186-gxs74wit.txt' === file2bib.sh === id: cord-308201-lavcsqov author: Desforges, Marc title: Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System? date: 2019-12-20 pages: extension: .txt txt: ./txt/cord-308201-lavcsqov.txt cache: ./cache/cord-308201-lavcsqov.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-308201-lavcsqov.txt' === file2bib.sh === id: cord-278684-txlvla0j author: Gonzalez–Dunia, Daniel title: Borna Disease Virus and the Brain date: 1998-01-30 pages: extension: .txt txt: ./txt/cord-278684-txlvla0j.txt cache: ./cache/cord-278684-txlvla0j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-278684-txlvla0j.txt' === file2bib.sh === id: cord-331268-kzy33hdb author: Lynch, Sharon G. title: Multiple sclerosis date: 1996-01-31 pages: extension: .txt txt: ./txt/cord-331268-kzy33hdb.txt cache: ./cache/cord-331268-kzy33hdb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-331268-kzy33hdb.txt' === file2bib.sh === id: cord-002757-upwe0cpj author: Sullivan, Kathleen E. title: Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies date: 2017-08-07 pages: extension: .txt txt: ./txt/cord-002757-upwe0cpj.txt cache: ./cache/cord-002757-upwe0cpj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002757-upwe0cpj.txt' === file2bib.sh === id: cord-017499-51yy7y9n author: Freye, Enno title: Mechanism of Action of Opioids and Clinical Effects date: 2008 pages: extension: .txt txt: ./txt/cord-017499-51yy7y9n.txt cache: ./cache/cord-017499-51yy7y9n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-017499-51yy7y9n.txt' === file2bib.sh === id: cord-275795-ee7qyw5h author: Monette, Anne title: T Lymphocytes as Measurable Targets of Protection and Vaccination Against Viral Disorders date: 2018-10-24 pages: extension: .txt txt: ./txt/cord-275795-ee7qyw5h.txt cache: ./cache/cord-275795-ee7qyw5h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-275795-ee7qyw5h.txt' === file2bib.sh === id: cord-022756-kdgo4rqb author: nan title: Hematopoietic Tumors date: 2012-11-28 pages: extension: .txt txt: ./txt/cord-022756-kdgo4rqb.txt cache: ./cache/cord-022756-kdgo4rqb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-022756-kdgo4rqb.txt' === file2bib.sh === id: cord-023143-fcno330z author: nan title: Molecular aspects of viral immunity date: 2004-02-19 pages: extension: .txt txt: ./txt/cord-023143-fcno330z.txt cache: ./cache/cord-023143-fcno330z.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023143-fcno330z.txt' === file2bib.sh === id: cord-022659-chwk2bs4 author: nan title: Abstracts: Poster session date: 2004-10-08 pages: extension: .txt txt: ./txt/cord-022659-chwk2bs4.txt cache: ./cache/cord-022659-chwk2bs4.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-022659-chwk2bs4.txt' === file2bib.sh === id: cord-015352-2d02eq3y author: nan title: ESPR 2017 date: 2017-04-26 pages: extension: .txt txt: ./txt/cord-015352-2d02eq3y.txt cache: ./cache/cord-015352-2d02eq3y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 8 resourceName b'cord-015352-2d02eq3y.txt' === file2bib.sh === id: cord-026031-hnf5vayd author: Ford, Richard B. title: Emergency Care date: 2009-05-21 pages: extension: .txt txt: ./txt/cord-026031-hnf5vayd.txt cache: ./cache/cord-026031-hnf5vayd.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-026031-hnf5vayd.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-023026-2r84ndzv author: nan title: Posters date: 2013-06-14 pages: extension: .txt txt: ./txt/cord-023026-2r84ndzv.txt cache: ./cache/cord-023026-2r84ndzv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 9 resourceName b'cord-023026-2r84ndzv.txt' === file2bib.sh === id: cord-009997-oecpqf1j author: nan title: 2018 ASPHO ABSTRACTS date: 2018-03-31 pages: extension: .txt txt: ./txt/cord-009997-oecpqf1j.txt cache: ./cache/cord-009997-oecpqf1j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 14 resourceName b'cord-009997-oecpqf1j.txt' === file2bib.sh === id: cord-257167-rz4r5sj7 author: nan title: Abstracts for the 29th Annual Meeting of the Japan Neuroscience Society (Neuroscience2006) date: 2006-12-31 pages: extension: .txt txt: ./txt/cord-257167-rz4r5sj7.txt cache: ./cache/cord-257167-rz4r5sj7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 17 resourceName b'cord-257167-rz4r5sj7.txt' Que is empty; done keyword-cns-cord === reduce.pl bib === id = cord-001332-dp6vzgef author = Hosking, Martin P. title = ELR(+) chemokine signaling in host defense and disease in a viral model of central nervous system disease date = 2014-06-17 pages = extension = .txt mime = text/plain words = 2736 sentences = 152 flesch = 31 summary = Intracranial infection of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the central nervous system (CNS) of susceptible strains of mice results in an acute encephalomyelitis, accompanied by viral replication in glial cells and robust infiltration of virus-specific T cells that contribute to host defense through cytokine secretion and cytolytic activity. Moreover, PMNs have been shown to enhance central nervous system (CNS) inflammation by disrupting blood brain barrier (BBB) integrity in animal models of spinal cord injury (SCI; Tonai et al., 2001; Gorio et al., 2007) , autoimmune demyelination (Carlson et al., 2008) , and JHMV-induced encephalomyelitis (Zhou et al., 2003) , while blocking or silencing of CXCR2 signaling mutes inflammation and tissue damage in mouse models in which PMN infiltration is critical to disease initiation (Kielian et al., 2001; Belperio et al., 2005; Londhe et al., 2005a,b; Strieter et al., 2005; Gorio et al., 2007; Wareing et al., 2007; Carlson et al., 2008) . cache = ./cache/cord-001332-dp6vzgef.txt txt = ./txt/cord-001332-dp6vzgef.txt === reduce.pl bib === id = cord-001017-4qfhltg4 author = Chatterjee, Dhriti title = Microglia Play a Major Role in Direct Viral-Induced Demyelination date = 2013-06-20 pages = extension = .txt mime = text/plain words = 6654 sentences = 312 flesch = 42 summary = Previous studies demonstrated that microglia can be persistently infected by neurotropic mouse hepatitis virus (MHV) which causes meningoencephalitis, myelitis with subsequent axonal loss, and demyelination and serve as a virus-induced model of human neurological disease multiple sclerosis (MS). In our current studies, we have used RSA59 infection in vivo, in vitro, and ex vivo as a model to understand whether MHV can directly infect CNS resident microglia and the mechanism of microglial activation in the induction of chronic demyelination. To confirm the RSA59-induced CNS inflammation, brain and spinal cord sections from day 7 (peak of inflammation) and day 30 (peak of demyelination) postinfected mice were stained with H&E or LFB and examined. While Iba1 immunofluorescence was observed in both gray and white matter, double fluorescence/immunofluorescence demonstrated dual labelling of EGFP (viral antigen) positive Iba1 positive microglia/macrophages were present only in the white matter of RSA59 infected mice (Figure 1 ). cache = ./cache/cord-001017-4qfhltg4.txt txt = ./txt/cord-001017-4qfhltg4.txt === reduce.pl bib === id = cord-002209-xs6qigg4 author = Kıray, Hülya title = The multifaceted role of astrocytes in regulating myelination date = 2016-09-17 pages = extension = .txt mime = text/plain words = 7509 sentences = 355 flesch = 35 summary = In experimental allergic encephalomyelitis (EAE), a widely used animal model of MS, where demyelination is induced by myelin antigens, administered together with adjuvant that contains bacterial components (Traugott and Lebon, 1988; Tsukada et al., 1991; Villarroya et al., 1996) , GFAP expression was seen on more numerous and much larger astrocytic processes in chronic lesions compared to normal appearing white matter (Webster et al., 1985; Eng et al., 1971) . The milder "activated" astrocytes can secrete a range of factors including; neurotrophic factors, growth factors, and cytokines that will stimulate re/myelination by promoting neuronal survival, neurite outgrowth, neurogenesis, and/ or oligodendrocyte precursor cell (OPC) survival, proliferation, and/or maturation. Conversely astrocytes that tend to have a more severe "reactive" phenotype, possibly induced by proinflammatory cytokines/CNS tissue damage, may secrete cytokines and chemokines that lead to myelin and oligodendrocyte damage in vitro, suppress remyelination, delay disease recovery in experimental autoimmune encephalomyelitis (EAE), and suppress myelination in myelinating embryonic rat mixed spinal cord cultures. Transplantation of ciliary neurotrophic factor-expressing adult oligodendrocyte precursor cells promotes remyelination and functional recovery after spinal cord injury cache = ./cache/cord-002209-xs6qigg4.txt txt = ./txt/cord-002209-xs6qigg4.txt === reduce.pl bib === id = cord-006824-btcdjmfp author = nan title = Key Note and State of the Art Lectures date = 2002-09-07 pages = extension = .txt mime = text/plain words = 7577 sentences = 377 flesch = 34 summary = In a prospective phase II trial, we treated 37 patients with high dose therapy and autologous bone marrow transplantation for follicular lymphoma in first complete or partial remission [6] . A comparison with similar autologous HCT recipients with NHL who had not been treated with the monoclonal antibody after transplantation indicates that Figure 1 : Overall survival, event-free survival and relapse following autologous bone marrow transplantation in 37 patients with follicular lymphoma during their first complete or first partial chemotherapy-induced remissions this new post-transplant therapy has contributed positively to the treatment outcome. In 1986, a first group of 17 patients (14 with NHL and three with Hodgkin's disease) was described indicating that extended disease-free long-term survival can be attained with high dose therapy followed by allogeneic transplantation utilizing hematopoietic cells obtained either from fully or closely matched related donors [9] . cache = ./cache/cord-006824-btcdjmfp.txt txt = ./txt/cord-006824-btcdjmfp.txt === reduce.pl bib === id = cord-016954-l3b6n7ej author = Young, Colin R. title = Animal Models of Multiple Sclerosis date = 2008 pages = extension = .txt mime = text/plain words = 9705 sentences = 495 flesch = 44 summary = The relative inaccessibility and sensitivity of the central nervous system (CNS) in humans preclude studies on disease pathogenesis, and so much of our understanding of infections and immune responses has been derived from experimental animal models. Viral models are immensely relevant since epidemiological studies suggest an environmental factor, and almost all naturally occurring CNS demyelinating diseases of humans and animals of known etiology are caused by a virus. The most widely studied models of MS are the experimental infections of rodents resulting in an inflammatory demyelinating disease in the CNS, such as Theiler's virus, mouse hepatitis virus, and Semliki Forest virus. Theiler's virus-induced demyelination, a model for human MS, bears several similarities to the human disease: an immune-mediated demyelination, involvement of CD4 + helper T cells and CD8 + cytotoxic T cells, delayed type hypersensitivity responses to viral antigens and autoantigens, and pathology. cache = ./cache/cord-016954-l3b6n7ej.txt txt = ./txt/cord-016954-l3b6n7ej.txt === reduce.pl bib === id = cord-002119-kl431ev6 author = Garcia, Elisa title = Cytokine and Growth Factor Activation In Vivo and In Vitro after Spinal Cord Injury date = 2016-06-23 pages = extension = .txt mime = text/plain words = 13445 sentences = 687 flesch = 41 summary = Specific inflammatory cytokines such as TNF , IL-1, and IL-6 are synthetized by various cells in the CNS and are known as mediators of the peripheral immune response 8 [118, 192] IL-4 (i) High levels 24 h AI, concentrations remain during 7 days and decrease 3 days AI (i) Neuroinflammatory regulation in various pathological conditions (ii) Confers regenerative properties to macrophages (iii) Controls free radical production in peripheral macrophages and microglia [166, [193] [194] [195] [196] [197] [198] [199] IL-13 (i) Detected 1 day AI (i) Macrophage activation onto M2 phenotype [166, 199] IP-10/CXCL10 (i) Expressed locally 30 [200, [205] [206] [207] Mediators of Inflammation 9 [200, [205] [206] [207] MCP1/CCL2 (i) Detected from 1 h AI with PL at 24 h and remains low up to 24 days AI (i) Macrophage and PMN infiltration mediator [106, 184, 200, 205, 206] min: minutes; AI: after injury; PL: peak levels. cache = ./cache/cord-002119-kl431ev6.txt txt = ./txt/cord-002119-kl431ev6.txt === reduce.pl bib === id = cord-005734-14ba78cz author = Bennett, Jami L. title = CCL2 transgene expression in the central nervous system directs diffuse infiltration of CD45(high)CD11b(+) monocytes and enhanced Theiler’s murine encephalomyelitis virus-induced demyelinating disease date = 2003 pages = extension = .txt mime = text/plain words = 7588 sentences = 361 flesch = 45 summary = title: CCL2 transgene expression in the central nervous system directs diffuse infiltration of CD45(high)CD11b(+) monocytes and enhanced Theiler's murine encephalomyelitis virus-induced demyelinating disease To test the hypothesis that the presence of CCL2 in the CNS could regulate an immune-mediated, macrophage-dependent demyelinating disease, we infected either control, JE32, or JE95 (described previously; Huang et al [2002] ) transgenic mice with TMEV and assessed the animals for resulting clinical paralysis. However, it could be possible that the presence of any virus in the CNS of CCL2-transgenic mice would be a sufficient stimulus to activate the accumulated macrophage pool, initiating inflammation and development of demyelinating disease. Further, the mCMV studies demonstrate that the accelerated disease observed in CCL2-transgenic mice is specific to TMEV infection and not due to a nonspecific activation of localized monocytes/macrophages by any virus introduced into the CNS. cache = ./cache/cord-005734-14ba78cz.txt txt = ./txt/cord-005734-14ba78cz.txt === reduce.pl bib === id = cord-002757-upwe0cpj author = Sullivan, Kathleen E. title = Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies date = 2017-08-07 pages = extension = .txt mime = text/plain words = 24212 sentences = 1364 flesch = 40 summary = The first section addresses general considerations, the second section profiles specific infections organized according to mechanism of transmission, and the third section focuses on unique phenotypes and unique susceptibilities in patients with PIDDs. This review does not address most parasitic diseases. In developing countries where polio is still endemic and oral polio vaccine is essential for eradicating the disease, it is of utmost importance that all PIDD patients and family members should not receive live oral polio (OPV) because of the reported prolonged excretion of the virus for months and even years [24] . As for host factors, although severe and fatal cases have been described in healthy immunocompetent hosts [129, 130] , there is evidence to suggest that children under the age of 10 [130] and immunocompromised hosts either secondary to hematologic malignancies, immunosuppressant treatment for organ transplantation, or HIV infection are at a greater risk to develop more severe disease with higher case fatality rates [131, 132] . cache = ./cache/cord-002757-upwe0cpj.txt txt = ./txt/cord-002757-upwe0cpj.txt === reduce.pl bib === id = cord-000725-rafwlw0t author = Hindinger, Claudia title = IFN-γ Signaling to Astrocytes Protects from Autoimmune Mediated Neurological Disability date = 2012-07-27 pages = extension = .txt mime = text/plain words = 5114 sentences = 243 flesch = 37 summary = Experimental autoimmune encephalomyelitis (EAE) was induced in transgenic mice expressing signaling defective dominant-negative interferon gamma (IFN-γ) receptors on astrocytes to determine the influence of inflammation on astrocyte activity. Inhibition of IFN-γ signaling to astrocytes did not influence disease incidence, onset, initial progression of symptoms, blood brain barrier (BBB) integrity or the composition of the acute CNS inflammatory response. GFAPcR1D and wt mice were compared at the peak of acute disease to determine if IFN-c signaling altered astrocyte activation or CNS inflammation. Despite elevated demyelination and axonal loss in the absence of IFN-c signaling to astrocytes, spinal cords showed no evidence of differential astrocyte activation by either immunohistochemistry (Fig. 4 ), or differences in GFAP mRNA expression during the peak of acute disease (Fig. 5 ). Although demyelination was increased in the CNS of GFAPcR1D mice, the extent of astrocyte activation associated with spinal cord white matter lesions was similar in both groups ( Fig. 6 ; ,60 GFAP + cells/mm 2 ). cache = ./cache/cord-000725-rafwlw0t.txt txt = ./txt/cord-000725-rafwlw0t.txt === reduce.pl bib === id = cord-009577-29u7pdpk author = Gonzalez‐Scarano, F. title = Molecular pathogenesis of neurotropic viral infections date = 2004-10-08 pages = extension = .txt mime = text/plain words = 6374 sentences = 294 flesch = 41 summary = To cause systemic illness, a virus must first enter the host animal, undergo primary replication at a site near its portal of entry, and then ultimately spread to distant target tissues, such as the central nervous system (CNS). An infecting animal virus faces two main blocks to penetration of the CNS or any other specific target organ: (1) a variety of barriers prevent the free access of viruses to target cells, and (2) even when these barriers are ineffective, only certain cell types will support the internalization and replication of a particular virus. Monoclonal antibody variants have been used to map the antigenic sites of the influenza hemagglutinin 122, 76, 771 and have been used successfully to define important regions of the cellular binding proteins of rabies virus, reovirus, coronaviruses, and the California serogroup-all CNS pathogens. Viruses bind to the plasma membrane of susceptible target cells through specific receptors which may be proteins (HIV), lipids (vesicular stomatitis virus), or contain sialic acid (reovirus, influenza) [21, 641. cache = ./cache/cord-009577-29u7pdpk.txt txt = ./txt/cord-009577-29u7pdpk.txt === reduce.pl bib === id = cord-007603-27m9wz0i author = Rall, Glenn F. title = A transgenic mouse model to assess the interaction of cytotoxic T lymphocytes with virally infected, class I MHC-expressing astrocytes date = 2002-11-11 pages = extension = .txt mime = text/plain words = 3682 sentences = 202 flesch = 52 summary = Functional antigen-presenting capacity was conferred by the D(b) transgene, as virus-infected primary astrocytes obtained from transgenic BALB/c mice (K(d)I(d)D(d)L(d)) expressing the D(b) molecule were lysed by D(b)-restricted anti-viral CTL. The central nervous system (CNS) has been considered an immune privileged site compared with other organs by virtue of the blood-brain barrier that restricts access of macromolecules and non-activated lymphoid cells from the periphery into the CNS parenchyma and because resident CNS cells such as neurons, oligodendrocytes and astrocytes express negligible to undetectable levels of class I major histocompatibility (MHC) molecules (reviewed in Lampson, 1987) . To establish transgenic mice with astroglial expression of an MHC class I molecule, a minigene encoding the MHC class I antigen D b was placed under the regulatory influence of a modified murine glial fibrillary acidic protein (GFAP) gene (Fig. 1) . cache = ./cache/cord-007603-27m9wz0i.txt txt = ./txt/cord-007603-27m9wz0i.txt === reduce.pl bib === id = cord-005393-rhji4io9 author = Popko, Brian title = The effects of interferon-γ on the central nervous system date = 1997 pages = extension = .txt mime = text/plain words = 7969 sentences = 418 flesch = 42 summary = A large portion of this article is devoted to the substantial circumstantial and experimental evidence that suggests that IFN-γ plays an important role in the pathogenesis of the demyelinating disorder multiple sclerosis (MS) and its animal model experimental allergic encephalomyelitis (EAE). For example, the genes encoding the gaunylate binding protein and the IgG Fc receptor are induced in this way: Other genes that are stimulated by IFN-~/, such as the class I and class II molecules of the major histocompatibility complex (MHC), require a longer period (several hours) before transcriptional induction is detected. Many of the pathological events Observed in MS and EAE, such as increased MHC expression, macrophage activation, increased expression of leukocyte adhesion molecules on blood-brain barrier endothelial cells (Olsson, 1992) , and reactive gliosis (Balasingam et al., 1994) , are consistent with the known effects of IFN-~,. (1984) demonstrated a dramatic increase in the expression of the MHC class I glycoprotein in astrocytes, neurons, oligodendrocytes and microglia following the delivery of IFN-y to the CNS of 2-dold mice. cache = ./cache/cord-005393-rhji4io9.txt txt = ./txt/cord-005393-rhji4io9.txt === reduce.pl bib === id = cord-004911-fbge8tkc author = Imrich, H. title = On the role of peripheral macrophages during active experimental allergic encephalomyelitis (EAE) date = 2001 pages = extension = .txt mime = text/plain words = 6033 sentences = 356 flesch = 51 summary = Severely and mildly diseased animals were analysed with respect to infiltration of T-cells, macrophages and upregulation of MHC class II molecules on microglia in the brain. Experimental allergic encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS) inducible in susceptible strains of rats by active immunisation with myelin basic protein (MBP) in adjuvant. To monitor such differences between diseased animals and animals without symptoms, leukocytes were isolated from the CNS and analysed by flow cytometry with regard to infiltrating T-cells (TCRϩ), macrophages (CD45 high ) and activation of resident microglia (CD45 low , MHC IIϩ). After immunisation of rats with MBP in CFA containing high dose of myc.T animals develop severe disease with high influx of T-cells and peripheral macrophages in brain tissue. After immunisation of rats with CFA containing low dose of myc.T, and constant concentrations of the autoantigen MBP animals failed to develop severe symptoms, nevertheless, they showed strong T-cell influx in brain parenchyma. cache = ./cache/cord-004911-fbge8tkc.txt txt = ./txt/cord-004911-fbge8tkc.txt === reduce.pl bib === === reduce.pl bib === id = cord-010187-ymhcfyxx author = Gromeier, Matthias title = Mouse neuropathogenic poliovirus strains cause damage in the central nervous system distinct from poliomyelitis date = 2005-03-25 pages = extension = .txt mime = text/plain words = 5144 sentences = 296 flesch = 42 summary = We report a comparison of the clinical course and the histopathological features of neurological disease resulting from intracerebral virus inoculation in normal micewith those of murine poliomyelitis in hPVR-tg mice. Histopathological analysis showed a diffuse encephalomyelitis induced by specific poliovirus serotype 2 isolates in normal mice, that affected neuronal cell populations without discrimination, whereas in hPVR-tg animals, damage was restricted to spinal motor neurons. 6 The hPVR is a highly glycosylated protein with an apparent molecular weight of 80kDa2 The animal model for poliomyelitis in hPVR-tg mice showed PV-induced damage of comparable anatomical distribution as in primates, 1°'11 an observation confirming views of the hPVR as the critical determinant conferring PV susceptibility. None of the normal mice injected with PVI(M) showed clinical signs of neurological damage, whereas inoculation of type 2 PV strains produced signs of CNS infection ( Table 2) . cache = ./cache/cord-010187-ymhcfyxx.txt txt = ./txt/cord-010187-ymhcfyxx.txt === reduce.pl bib === id = cord-002021-67ao8chx author = Kim, Seong Bum title = Blockage of indoleamine 2,3-dioxygenase regulates Japanese encephalitis via enhancement of type I/II IFN innate and adaptive T-cell responses date = 2016-04-18 pages = extension = .txt mime = text/plain words = 12049 sentences = 601 flesch = 51 summary = Because viral loads at the periphery in IDO-ablated mice were lower than in wild-type BL/6 mice, we evaluated the contribution of DC subsets (conventional and plasmacytoid) and macrophages to the IFN-I innate immune responses caused by JEV infection in the IDOablated environment. IDO-ablated BMDCs and pDCs, but not BMDMs, showed rapid induction of IFN-α/β in response to JEV infection compared to levels measured in cells from wild-type BL/6 mice. Collectively, IDO ablation appears to provide rapid and increased responses of IFN-I innate immunity in myeloid-derived DCs and pDCs upon JEV infection, thereby contributing to the amelioration of JE through early control of viral replication. Therefore, we examined viral replication and IFN-I innate immune responses in primary cortical neuron cells generated from wild-type BL/6 and IDO-ablated mice after JEV infection. cache = ./cache/cord-002021-67ao8chx.txt txt = ./txt/cord-002021-67ao8chx.txt === reduce.pl bib === id = cord-010016-fs8pjy1z author = WEBB, H. E. title = CAN VIRAL ENVELOPE GLYCOLIPIDS PRODUCE AUTO‐IMMUNITY, WITH REFERENCE TO THE CNS AND MULTIPLE SCLEROSIS? date = 2008-05-12 pages = extension = .txt mime = text/plain words = 2976 sentences = 154 flesch = 47 summary = In this paper it is proposed that CNS demyelination could arise in susceptible individuals (HLA type) from an immune response to glycolipids, triggered by the carrier effect of one or more enveloped neurotropic viruses. The demyelination is dependent upon T-lymphocytes probably cytotoxic cells (Jagelman et al., 1978; Fazakerley, Amor & Webb 1983; Pathak et al., 1983) and probably results from an immune reaction against viral antigens on the surface of oligodendrocytes or myelin. Since all are budding viruses they will have a similar host derived viral envelope provided the virus replicates in the same cell type. It is an intriguing possibility that CNS demyelination in diseases such as MS, arises as a result of an auto-immune reaction against specific glycolipids, induced by the carrier effect of a budding neurotropic virus. I n this way any number of enveloped neurotropic viruses could be involved in initiating and restimulating a n autoimmune response to the same brain cell membrane specific glycolipid(s). cache = ./cache/cord-010016-fs8pjy1z.txt txt = ./txt/cord-010016-fs8pjy1z.txt === reduce.pl bib === id = cord-011533-im78xwl8 author = Gloude, Nicholas J. title = Thinking Beyond HLH: Clinical Features of Patients with Concurrent Presentation of Hemophagocytic Lymphohistiocytosis and Thrombotic Microangiopathy date = 2020-05-23 pages = extension = .txt mime = text/plain words = 4879 sentences = 262 flesch = 37 summary = MODS was diagnosed when a patient had symptoms of HLH/TMA and dysfunction of two or more organ systems: renal failure requiring renal replacement therapy (RRT) or cystatin C glomerular filtration rate (GFR) < 50 mL/min, invasive or non-invasive positive pressure ventilator support for > 24 h, diagnosis of pulmonary hypertension (as determined by echocardiogram and cardiology consultation), serositis (pleural or pericardial effusions), severe hypertension requiring either ≥ 2 medications or continuous infusion of an antihypertensive for > 12 h to maintain blood pressure < 99% for age, CNS symptoms (seizures, bleeding, posterior reversible encephalopathy syndrome (PRES), or altered mental status), or gastrointestinal symptoms (ileus and/or bleeding) [20] [21] [22] [23] [24] . We observed a high incidence of clinically significant complement-mediated thrombotic microangiopathy (TMA) associated with multi-organ injury in children and young adults with a diagnosis of HLH. cache = ./cache/cord-011533-im78xwl8.txt txt = ./txt/cord-011533-im78xwl8.txt === reduce.pl bib === id = cord-008523-avkgldnp author = Perlman, Stanley title = Selection of and evasion from cytotoxic T cell responses in the central nervous system date = 2004-01-07 pages = extension = .txt mime = text/plain words = 8866 sentences = 401 flesch = 44 summary = In mice that were transgenic for a T cell receptor (TCR) specific for lymphocytic choriomeningitis virus (LCMV), infection with LCMV resulted in the rapid appearance of virus mutated in the target CTL epitope. In these mice, CTLs recognizing multiple epitopes are detected, suggesting that an immune response directed against several epitopes precluded the selection of CTL escape mutants, at least in settings in which virus clearance was relatively efficient. One of the best examples of a pathological setting in which CTL escape mutants contribute to virus persistence and the development of disease is that of mice infected with the neurotropic coronavirus, mouse hepatitis virus--strain JHM (MHV-JHM). These results suggest that CTL escape mutants are critical in virus persistence and in the development of clinical disease in mice infected with MHV-JHM. The selection of CTL escape mutants in the CNS of MHV-infected mice demonstrates that MHV infection of a cell expressing MHC class I antigen is a critical part of the pathogenic process. cache = ./cache/cord-008523-avkgldnp.txt txt = ./txt/cord-008523-avkgldnp.txt === reduce.pl bib === === reduce.pl bib === id = cord-018042-qt7055fw author = Müller, Marcus title = Chemokine Actions in the CNS: Insights from Transgenic Mice date = 2008 pages = extension = .txt mime = text/plain words = 5804 sentences = 268 flesch = 42 summary = So while constitutive, astrocyte-targeted production of CXCL10 can promote the recruitment of leukocytes to the CNS, this chemokine lacks the ability to further influence these cells, in particular, to drive a functional immune response. Although it has been possible to produce stimulus-evoked encephalopathy in MBP-and GFAP-CCL2 transgenic mice by systemic innate immune challenge these disorders are largely transient and therefore do not model the increased levels of CNS CCL2 that have been reported to occur in chronic neurological diseases such as human immunodeficiency virus type 1-associated dementia, amyotrophic lateral sclerosis, and multiple sclerosis. It is speculated that CCL21 derived from transgenic oligodendrocytes in the brain of the MBP-CCL21 mice may have interacted with CXCR3 on microglia inducing an inflammatory response that led to the influx of inflammatory cells into the CNS. Functional expression of the lymphoid chemokines CCL19 (ELC) and CCL 21 (SLC) at the blood-brain barrier suggests their involvement in G-protein-dependent lymphocyte recruitment into the central nervous system during experimental autoimmune encephalomyelitis cache = ./cache/cord-018042-qt7055fw.txt txt = ./txt/cord-018042-qt7055fw.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-017917-7aeh6quc author = Marten, Norman W. title = The Role of Metalloproteinases in Corona Virus Infection date = 2005 pages = extension = .txt mime = text/plain words = 3000 sentences = 148 flesch = 38 summary = A number of MMPs and TIMPs have also been associated with the CNS inflammatory/demyelinating disease multiple sclerosis (MS) in humans (2,32) as well as its rodent model experimental autoimmune encephalitis (EAE) (10,38). The consistent association of MMP and TIMP expression with inflammatory demyelinating disease suggests that MMPs play either a direct or indirect role in promoting CNS pathology (2,27,32). However, subsequent analysis of individual cell populations sorted from infected brains indicated that MMP-9 gene expression is up regulated several fold among infiltrating inflammatory cells (Zhou, unpublished data) (Table 1) . Thus, MMP-9 from neutrophils is regulated at the level of degranulation as opposed to gene transcription and co-expression of TIMPs. These data suggest MMP-9 is likely released from both mononuclear and polymorphonuclear infiltrates during JHMV infection. Cell surface binding and activation of gelatinase A induced by expression of membrane-type-l-matrix metalloproteinase (MT1-MMP) cache = ./cache/cord-017917-7aeh6quc.txt txt = ./txt/cord-017917-7aeh6quc.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-017499-51yy7y9n author = Freye, Enno title = Mechanism of Action of Opioids and Clinical Effects date = 2008 pages = extension = .txt mime = text/plain words = 24955 sentences = 1278 flesch = 45 summary = Thus, -selective opioids like morphine, fentanyl and sufentanil, due to the high density of binding sites, mediate their main action within the brain stem and the midbrain. This sterospecificity of opiate action supports the concept of selective receptor binding to a site, which is able to distinguish in "handedness or goodness of fit" of an opioid molecule maximal response induced by administration of the active agent. On the other hand mixed agonist/antagonists, such as pentazocine, nalorphine, levallorphan, nalbuphine and butorphanol, demonstrate characteristics, which enable them to displace a pure agonist at the receptor site (antagonistic effect), but at the same time when administered by themselves, they induce opioid related effects such as analgesia and respiratory depression (agonistic effects; Table II-7) . However, a less potent opioid like codeine or tramadol, even when given in dosages higher than their therapeutic margin, will not induce a clinically relevant respiratory depressive effect ( Figure II-34) . cache = ./cache/cord-017499-51yy7y9n.txt txt = ./txt/cord-017499-51yy7y9n.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-022395-rk31pwoa author = Schuller-Levis, Georgia title = Central Nervous System: Viral Infection and Immune-Mediated Inflammation date = 2012-12-02 pages = extension = .txt mime = text/plain words = 8843 sentences = 471 flesch = 41 summary = Acute and chronic relapsing EAE can be induced in laboratory animals by an injection of CNS tissue, CNS myelin, myelin basic protein, or more recently, T-cell lines specific for nervous system antigens. Infection with mouse hepatitis virus (MHV), has been shown to block expression of MHC molecules on murine cerebral endothelial cells (see later discussion) (Joseph et al., 1991) . Until recently, the HLA Class I molecules were thought to be the primary, if not the only, HLA recognition structure for CTLs. Studies of measles and Epstein-Barr virus (EBV) infection suggest that HLA Class II molecules can also serve as recognition sites, further expanding the potential action of CTLs. Viral antigens recognized by CTLs have also been expanded beyond the traditional cell surface molecules (Braciale and Braciale, 1986) . The subsequent activation of specific cellular transcription factors in response to extracellular stimuli can induce the expression of virus and lead to CNS disease. Immune response gene products (la antigens) on glial and endothelial cells in virus-induced demyelination cache = ./cache/cord-022395-rk31pwoa.txt txt = ./txt/cord-022395-rk31pwoa.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-022756-kdgo4rqb author = nan title = Hematopoietic Tumors date = 2012-11-28 pages = extension = .txt mime = text/plain words = 42445 sentences = 2381 flesch = 43 summary = Hepatosplenic lymphoma is a relatively uncommon, distinct presentation in the dog marked by a lack of significant peripheral lymphadenopathy in the face of hepatic, splenic, and bone marrow infiltration with malignant lymphocytes, usually of T-cell origin. In a randomized study of 60 dogs with lymphoma comparing CHOP-based chemotherapy with CHOPbased chemotherapy and a human granulocyte-macrophage colony-stimulating factor (GM-CSF) DNA cationic-lipid complexed autologous whole tumor cell vaccine, a small measure of immunomodulation was documented by delayed-type hypersensitivity; however, significant improvement in clinical outcome was not noted. 263 Total body irradiation (and/or ablative chemotherapy) for complete or partial bone marrow ablation followed by reconstitution with bone marrow or stem-cell transplant in dogs, although a recognized model in comparative research settings, 264,265 is still in its early phases of development and application in clinical veterinary It is associated with slow progression and long-term survival following corticosteroid management; however, it does have the potential to progress to high-grade lymphoma. cache = ./cache/cord-022756-kdgo4rqb.txt txt = ./txt/cord-022756-kdgo4rqb.txt === reduce.pl bib === id = cord-267166-ecmayzr6 author = Savarin, Carine title = Distinct Gene Profiles of Bone Marrow-Derived Macrophages and Microglia During Neurotropic Coronavirus-Induced Demyelination date = 2018-06-11 pages = extension = .txt mime = text/plain words = 7736 sentences = 371 flesch = 39 summary = While gene expression in CNS infiltrating BMDM was upregulated early following infection and subsequently sustained, microglia expressed a more dynamic gene profile with extensive mRNA upregulation coinciding with peak demyelination after viral control. This study takes advantage of the distinct tissue environments established during EAE and JHMV infection to characterize temporal alterations in gene expression profiles of BMDM versus microglia in a Th1 biased demyelination model. We next evaluated effector functions of BMDM versus microglia associated with JHMV-induced demyelination by comparing gene expression profiles using nCounter analysis of mRNA isolated from purified BMDM and microglia of infected CX3CR1 GFP/+ CCR2 RFP/+ mice. Using a similar approach with Nanostring analysis as in EAE, the present study used gene expression profiling to characterize both BMDM and microglia myeloid functions at various times post JHMV infection. cache = ./cache/cord-267166-ecmayzr6.txt txt = ./txt/cord-267166-ecmayzr6.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-104265-kcygxo7h author = Brabb, Thea title = In Situ Tolerance within the Central Nervous System as a Mechanism for Preventing Autoimmunity date = 2000-09-18 pages = extension = .txt mime = text/plain words = 7106 sentences = 303 flesch = 52 summary = Animal models of MS have shown that CNS-specific T cells are present in the peripheral T cell repertoire of healthy mice and cause autoimmune disease only when they are activated by immunization. Strikingly, transgenic T cells isolated from the CNS that are specific for myelin basic protein (MBP) are also primarily phenotypically naive but are unresponsive to antigenic stimulation in vitro. Our data demonstrate that as MBP TCR transgenic mice age, an increasing number of T cells expressing MBP-specific TCRs are activated and converted to a memory phenotype in the absence of spontaneous EAE. In addition, naive CD4 ϩ T cells specific for non-CNS antigens proliferate equally well when they are isolated from either the CNS or LNs, and it is only T cells from MBP TCR transgenic mice that are nonresponsive. Despite tolerance induction of naive MBP-specific CNS T cells, spontaneous EAE still occurs in a percentage of the MBP TCR transgenic mice, primarily within an age window of 5-12 wk (14) . cache = ./cache/cord-104265-kcygxo7h.txt txt = ./txt/cord-104265-kcygxo7h.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-264794-bgygebgx author = Lundgren, A.-L. title = Feline non-suppurative meningoencephalomyelitis. A clinical and pathological study date = 1992-11-30 pages = extension = .txt mime = text/plain words = 4861 sentences = 288 flesch = 48 summary = It has been argued that the syndrome may include several aetiologically unrelated conditions affecting the central nervous system of cats, e.g. toxoplasmosis (Hirth and Nielsen, 1969) and the cerebral form of feline infectious peritonitis (Slauson and Finn, 1972; Kornegay, 1978) . Histopathological examination revealed throughout the central nervous system a non-suppurative inflammation characterized by perivascular mononuclear cuffing, presence of inflammatory nodules and neuronal degeneration in all cats. Neuropathological examination of the cats of the present study showed a marked inflammatory reaction in the cerebral leptomeninges as well as in the grey matter of the brain and spinal cord. Neither the serological results nor the clinical and histopathological findings in the cats with staggering disease indicate a FeLV infection. Feline immunodeficiency virus (FIV) has emerged as an important cause of neurological disease in cats (Dow, Poss and Hoover, 1990; Sparger, 1991) , often in association with clinical syndromes typical of an immunodeficient state (chronic stomatitis, enteritis, dermatitis, etc). cache = ./cache/cord-264794-bgygebgx.txt txt = ./txt/cord-264794-bgygebgx.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-270458-7imgvale author = Franchini, Massimo title = The impact of the SARS‐CoV‐2 outbreak on the safety and availability of blood transfusions in Italy date = 2020-04-13 pages = extension = .txt mime = text/plain words = 1525 sentences = 78 flesch = 50 summary = The CNS has already released since 22 January 2020 a recommendation outlining preventative measures for the transmission of SARS-CoV-2 by transfusion of labile blood components related to travels from the People's Republic of China. On 2 March 2020, following the recommendations of the European Centre for Disease Prevention and Control (ECDC) [9] and reflecting the decrees of the Italian government, the CNS updated the prevention measures, reducing the period of temporary deferral of donors from the previous 28 to 14 days. Following the declaration of the government of the widespread dissemination of the SARS-CoV-2 infection in Italy, the last update of the CNS on 10 March 2020 extended these measures to the whole national territory of Italy. In Fig. 1 , the trend of positive cases for SARS-CoV-2 infection in Italy, updated on 20 March 2020, is reported with a concise chronology of the main documents released and the trend of blood donations in the same period. cache = ./cache/cord-270458-7imgvale.txt txt = ./txt/cord-270458-7imgvale.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-023143-fcno330z author = nan title = Molecular aspects of viral immunity date = 2004-02-19 pages = extension = .txt mime = text/plain words = 43425 sentences = 2056 flesch = 47 summary = Based on a variety of experimental evidence, it is clear that demyelination induced in SJUJ mice by infection with the BeAn strain of TMEV is a Thl-mediated event: (a) disease induction is suppressed in T cell-deprived mice and by in vivo treatment with anti-I-A and anti-CD4 antibodies; (b) disease susceptibility correlates temporally with the development of TMEV-specific, MHC-class Il-restricted DTH responses and with a predominance of anti-viral lgG2a antibody; (c) activated (Le., lL-2RC) T cells infiltrating the CNS are exclusively of the CD4+ phenotype, and (d) proinflammatory cytokines (IFNq and TNF-p) are predominantly produced in the CNS. These results have important implications for a possible viral trigger in MS as they indicate that chronic demyelination in TMEV-infected mice is initiated in the absence of demonstrable neuroantigen-specific autoimmune responses and are consistent with a model wherein early myelin damage is mediated via primarily by mononuclear phagocytes recruited to the CNS and activated by pro-inflammatory cytokines produced by TMEV-specific Thl cells. cache = ./cache/cord-023143-fcno330z.txt txt = ./txt/cord-023143-fcno330z.txt === reduce.pl bib === id = cord-022659-chwk2bs4 author = nan title = Abstracts: Poster session date = 2004-10-08 pages = extension = .txt mime = text/plain words = 49153 sentences = 2598 flesch = 49 summary = We investigated the usefulness of informant-based data in Alzheimer's disease (AD) by comparing caregivers' subjective evaluations of 83 probable A D patients' performance on an abbreviated version of the Memory Self-Report Questionnaire to objective evaluations derived from an extensive battery of neuropsychological tests and to clinicians' evaluations. Compared with 89 subjects (mean age 75.2 yr; 34 men, 55 women) with dementia of the Alzheimer type (DAT), there were no significant group differences for comparable Clinical Dementia Rating stages of dementia for measures of language, Activities of Daily Living, or general cognition. The mean age at onset did not differ significantly between handedness groups (F [ l,lOO] = .82), but the mean duration of symptoms ( Alterations in the optical properties of brain can be used to detect pathological changes in patients with Alzheimer's disease (AD). cache = ./cache/cord-022659-chwk2bs4.txt txt = ./txt/cord-022659-chwk2bs4.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-266441-sd117tzs author = Almutrafi, Amna title = The Epidemiology of Primary Central Nervous System Tumors at the National Neurologic Institute in Saudi Arabia: A Ten-Year Single-Institution Study date = 2020-02-15 pages = extension = .txt mime = text/plain words = 2589 sentences = 149 flesch = 50 summary = OBJECTIVES: This study is aimed at describing the epidemiological trends of primary CNS tumors in children and adults at the National Neurologic Institute in Saudi Arabia. The worldwide incidence age-standardized rates (ASR) of brain and nervous system cancer in high/very-high HDI (Human Development Index) regions versus low/medium HDI regions was 5.0 and 2.4 for men and 4.0 and 1.7 for women (Saudi Arabia is classified as very-high HDI according to the United Nations Development Program 4-tier system), respectively. Medulloblastomas were the most commonly reported histology type in the pediatric age group followed by low5 Journal of Cancer Epidemiology grade gliomas with a predominance of pilocytic astrocytoma. This study contains the largest institution-based ICD-O and WHO-classified epidemiological analysis of malignant and nonmalignant primary brain tumors in Saudi Arabia in adult and pediatric groups. With regard to a single tumor entity, meningioma was the most common primary brain tumor in adults while in the pediatric age group, medulloblastoma was the leading histology. cache = ./cache/cord-266441-sd117tzs.txt txt = ./txt/cord-266441-sd117tzs.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-015352-2d02eq3y author = nan title = ESPR 2017 date = 2017-04-26 pages = extension = .txt mime = text/plain words = 82253 sentences = 4479 flesch = 46 summary = Lapierre; Montreal/CA Summary: Objectives: To review the classification of visceroatrial situs To describe the associated cardiac and non-cardiac anomalies To illustrate typical findings in fetuses, neonates and children To discuss the surgical consideration and the long-term follow-up in these patients Abstract: By definition, the type of situs is determined by the relationship between the atria and the adjacent organs. As is often the case, radiology in JIA is all about: knowing your clinicians (i.e. the pretest likelihood for disease) being technically eloquent (e.g. using high-resolution US probes, not delaying post-contrast MRI acquisitions) knowing what is normal (e.g. normal undulations in the articular surface, focal bone marrow signal variation) not being dogmatic about individual observations or measurements interpreting your findings in a clinical context The lecture will demonstrate similarities and differences among joints and modalities in children with variable-severity JIA. cache = ./cache/cord-015352-2d02eq3y.txt txt = ./txt/cord-015352-2d02eq3y.txt === reduce.pl bib === === reduce.pl bib === id = cord-271011-5stsx5je author = Singh, M. title = Inflammatory cerebrospinal fluid analysis in cats: clinical diagnosis and outcome date = 2005-03-09 pages = extension = .txt mime = text/plain words = 6930 sentences = 400 flesch = 53 summary = The purpose of this study was to determine if signalment, clinical signs, CSF analysis, additional clinicopathological data and diagnostic imaging could be used to determine the specific aetiology of the CNS disease in cats with inflammatory CSF. Based on the results, clinical information, clinical pathology and ancillary testing procedures the following classifications of disease could be made: 1, feline infectious peritonitis (FIP); 2, Cryptococcus species infection; 3, Toxoplasma species infection; 4, other meningoencephalitis; 5, thiamine deficiency; 6, lymphoma; 7, other neoplasia; 8, trauma; 9, intervertebral disc disease; 10, spinal cord granuloma and 11, undiagnosed (Table 2) . A presumptive diagnosis of FIP was made based on age, a suppurative or mixed inflammatory CSF, poor response to treatment, elevated serum or body cavity effusion FeCoV antibody titre or a reduced albumin:globulin ratio (!0.5) of serum or body cavity effusions. A presumptive diagnosis was made based on a mild suppurative-mixed CSF inflammation, normal-mildly increased CSF protein levels and positive IgG antibody titre. cache = ./cache/cord-271011-5stsx5je.txt txt = ./txt/cord-271011-5stsx5je.txt === reduce.pl bib === id = cord-278684-txlvla0j author = Gonzalez–Dunia, Daniel title = Borna Disease Virus and the Brain date = 1998-01-30 pages = extension = .txt mime = text/plain words = 13952 sentences = 784 flesch = 43 summary = The BDV paradigm is amenable to study virus–cell interactions in the CNS that can lead to neurodevelopmental abnormalities, immune-mediated damage, as well as alterations in cell differentiated functions that affect brain homeostasis. Evidence provided by epidemiological and clinical data, together with virological studies, have led to the hypothesis that chronic viral infections of the CNS contribute to human mental disorders of unknown etiology. Therefore, neuronal damage seen in BD appears to be mediated by the cytotoxic activity of CD8 ϩ T-cells present in the brain parenchyma of BDV-infected rats. Studies on PTI-NB rats may provide valuable information regarding the contribution of CNS resident cells to disturbances in cytokine gene expression caused by BDV. Borna disease virus replicates in astrocytes, Schwann cells and ependymal cells in persistently infected rats: Location of viral genomic and messenger RNAs by in situ hybridization Expression of tissue factor is increased in astrocytes within the central nervous system during persistent infection with Borna disease virus cache = ./cache/cord-278684-txlvla0j.txt txt = ./txt/cord-278684-txlvla0j.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-280987-uhxk5b1b author = Turtle, L. title = Encephalitis, Viral date = 2014-05-01 pages = extension = .txt mime = text/plain words = 2266 sentences = 120 flesch = 33 summary = Encephalitis is inflammation and swelling of the brain, often caused by an acute viral infection, or a paraor postinfectious phenomenon known as acute disseminated encephalomyelitis (ADEM). The term includes both viral infections of the brain with predominantly gray matter disease and acute disseminated encephalomyelitis (ADEM), an immune-mediated demyelinating disease. Clinically, acute viral encephalitis and ADEM usually manifest with fever, severe headache, neck stiffness, alterations of consciousness, focal neurological signs, and often seizures, especially in children. Once permissive host cells are infected in the subcutaneous tissue, the mucous membranes, or the hematopoietic system (particularly macrophages), viruses replicate usually locally before there is invasion of the central nervous system (CNS). Enteroviruses and mumps virus infect primarily meningeal and ependymal cells; therefore, they usually cause benign meningitis and only rarely are associated with encephalitis. On rare occasions when arboviruses infect the brain, they usually cause encephalitis with a significant death rate; thus, these viruses are not highly neuroinvasive but are highly neurotropic (and neuronotropic) and neurovirulent. cache = ./cache/cord-280987-uhxk5b1b.txt txt = ./txt/cord-280987-uhxk5b1b.txt === reduce.pl bib === === reduce.pl bib === id = cord-297448-aiorjsyh author = Atkinson, Jeffrey R. title = Dynamics of Virus-Specific Memory B Cells and Plasmablasts following Viral Infection of the Central Nervous System date = 2019-01-04 pages = extension = .txt mime = text/plain words = 7702 sentences = 393 flesch = 52 summary = During infection with a gliatropic mouse hepatitis virus (MHV) derived from the JHM strain (JHMv2.2-1), IgDpositive (IgD ϩ ) (naive/transitional) B cells prevail early, but they decrease coincident with increasing proportions of CD138 ϩ antibody (Ab)-secreting cells (ASC) and CD138 Ϫ IgG ϩ isotype-switched memory B cells (Bmem) as germinal centers (GCs) are formed in draining lymph nodes (1, 2) . To better characterize the proportions of virus-specific Bmem and ASC accumulating in the CLN and the CNS following viral encephalomyelitis, we took advantage of mice expressing tamoxifen-inducible Cre recombinase (Cre-ERT2) under the Aicda promoter crossed with Rosa26-loxP-tdTomato reporter mice to obtain progeny in which AIDexpressing cells can be identified by fluorescence following tamoxifen administration (4, 27) . Comparison of total numbers of tdTomato ϩ cells and their compositions of ASC and Bmem in brains and spinal cords over time following infection revealed overall similar kinetics of virus-specific B cell accumulation (Fig. 5B) . cache = ./cache/cord-297448-aiorjsyh.txt txt = ./txt/cord-297448-aiorjsyh.txt === reduce.pl bib === id = cord-272981-8gahvdt0 author = Wege, Helmut title = Relapsing subacute demyelinating encephalomyelitis in rats during the course of coronavirus JHM infection date = 1984-08-31 pages = extension = .txt mime = text/plain words = 3725 sentences = 295 flesch = 57 summary = These results demonstrate that mutants of JHM virus can induce a relapsing demyelinating disease process, associated with a persistent infection, which possesses some similarities to chronic experimental allergic encephalomyelitis. It has been shown that an autoimmune reaction against CNS tissue can lead to 6hronic relapsing demyelination as seen in chronic experimental allergic encephalomyelitis (EAE) whereas the role of a virus infection in the induction of such a condition has not so far been directly demonstrated (McFarlin et al. After virus infection in rats inflammatory disseminating CNS lesions of marked demyelination develop accompanied by clinical signs of a subacute disease after varying incubation times. The induction of a progressive demyelinating, or relapsing demyelinating, disease process, in JHM virus-infected rats has ~me parallels to chronic EAE, an animal model based on sensitation ~8ainst CNS tissue extracts or myelin basic protein (McFarlin et al. cache = ./cache/cord-272981-8gahvdt0.txt txt = ./txt/cord-272981-8gahvdt0.txt === reduce.pl bib === id = cord-269861-r07osd0w author = Kim, Jin Hyoung title = CCR5 ameliorates Japanese encephalitis via dictating the equilibrium of regulatory CD4(+)Foxp3(+) T and IL-17(+)CD4(+) Th17 cells date = 2016-07-20 pages = extension = .txt mime = text/plain words = 12067 sentences = 720 flesch = 60 summary = Our results also revealed that adoptive transfer of sorted CCR5(+)CD4(+)Foxp3(+) Tregs into Ccr5(−/−) mice could ameliorate JE progression without apparently altering the viral burden and CNS infiltration of IL-17(+)CD4(+) Th17 cells, myeloid-derived Ly-6C(hi) monocytes and Ly-6G(hi) granulocytes. The frequency and absolute number of CD4 + Foxp3 + Tregs (a, c), IFN-γ + CD4 + Th1, and IL-17 + CD4 + Th17 cells (b, d) in the spleen (a, b) and brain (c, d) of Ccr5 +/+ and Ccr5 −/− mice were determined by flow cytometric analysis at 3 and 5 days following JEV (3.0 × 10 7 pfu) infection. Although our results suggest that the increased number of CD4 + Foxp3 + Tregs in extraneural lymphoid tissue and the CNS of Ccr5 +/+ mice is associated with mild JE, we did not provide direct evidence regarding whether the enhanced response of CD4 + Foxp3 + Tregs plays a beneficial role in JE progression. cache = ./cache/cord-269861-r07osd0w.txt txt = ./txt/cord-269861-r07osd0w.txt === reduce.pl bib === id = cord-299051-5r2s8z1a author = Tsuhako, Maria Heloisa title = Tempol ameliorates murine viral encephalomyelitis by preserving the blood–brain barrier, reducing viral load, and lessening inflammation date = 2010-03-01 pages = extension = .txt mime = text/plain words = 5935 sentences = 308 flesch = 44 summary = Furthermore, treatment with tempol decreased CNS viral titers, macrophage and T lymphocyte infiltration, and levels of markers of inflammation, such as expression of inducible nitric oxide synthase, transcription of tumor necrosis factor-α and interferon-γ, and protein nitration. Immunohistochemical analysis of the brain (Fig. 6 ) and spinal cord (data not shown) tissues showed that viral infection resulted in macrophage infiltration, iNOS expression, and protein nitration, all of which were greatly attenuated by tempol treatment. Semiquantitative image analysis of the immunostaining of the brain tissues revealed that treatment with tempol reduced macrophage infiltration, iNOS expression, and 3nitrotyrosine levels to about 4, 26, and 16% of those of untreated mice, respectively (Fig. 7A) . In comparison, tempol is more effective than uric acid in scavenging nitric oxide-derived oxidants [9] , displays low toxicity in animal models [15, 16] , permeates the blood-brain barrier (Fig. 2) , and inhibits the enzyme myeloperoxidase ( [20] ; see Augusto et al., [53] , which has been recently associated with MS [54, 55] . cache = ./cache/cord-299051-5r2s8z1a.txt txt = ./txt/cord-299051-5r2s8z1a.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-275795-ee7qyw5h author = Monette, Anne title = T Lymphocytes as Measurable Targets of Protection and Vaccination Against Viral Disorders date = 2018-10-24 pages = extension = .txt mime = text/plain words = 28265 sentences = 1205 flesch = 38 summary = We focus on immunity generated against both natural infection and vaccination, where a steady shift in conferred vaccination immunogenicity is observed from quantifying activated and proliferating, long-lived effector memory T cell subsets, as the prominent biomarkers of long-term immunity against viruses and their associated disorders causing high morbidity and mortality rates. Since that time, the occurrence of epidemics and outbreaks are now at lower risk, following the introduction of massive vaccination programs able to induce immune system targeting of viruses causing severe disorders affecting distinct geographical locations, and with many epidemiological reports demonstrating long-term efficacy of viral control of non-naïve populations. This approach is being developed to use virus-infected cell-killing antibodies that produce an antiviral environment; these termed antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, which are predicted to link innate and adaptive immune responses, and is becoming possible due to new technologies for rapid isolation and characterization of monoclonal antibodies targeting conserved regions of influenza virus, reviewed in Jegaskanda et al. cache = ./cache/cord-275795-ee7qyw5h.txt txt = ./txt/cord-275795-ee7qyw5h.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-311845-wnk7itha author = Lubetzki, Catherine title = Demyelination in multiple sclerosis date = 2014-02-05 pages = extension = .txt mime = text/plain words = 7400 sentences = 345 flesch = 37 summary = Whereas multiple sclerosis was long considered as a T cell-mediated disease, the role of B lymphocytes is now increasingly recognized, and the influence of antibodies on tissue damage actively investigated. Multiple sclerosis (MS) is generally considered as an autoimmune disease, in which autoreactive T cells enter the central nervous system (CNS) from the peripheral circulation and induce an inflammatory cascade resulting in demyelination and axonal loss. Nevertheless, vesicular disruption of myelin seen in highly active MS lesions was found to be associated with anti-MOG and MBP antibodies, suggesting that demyelination might be causally related to the deposition of antigen-specific autoantibodies (Genain et al., 1999) . Recent findings have suggested that, following a primary oligodendrocyte or myelin injury, local APCs could process myelin antigens and traffic from the CNS to secondary lymphoid organs, where they may induce or enhance an adaptive demyelinating immune reaction. cache = ./cache/cord-311845-wnk7itha.txt txt = ./txt/cord-311845-wnk7itha.txt === reduce.pl bib === === reduce.pl bib === id = cord-299967-90aknp7c author = Terry, Rachael L title = Inflammatory monocytes and the pathogenesis of viral encephalitis date = 2012-12-17 pages = extension = .txt mime = text/plain words = 6111 sentences = 327 flesch = 35 summary = Monocytes are a heterogeneous population of bone marrow-derived cells that are recruited to sites of infection and inflammation in many models of human diseases, including those of the central nervous system (CNS). Ly6C(hi)/CCR2(hi) inflammatory monocytes have been identified as the circulating precursors of brain macrophages, dendritic cells and arguably microglia in experimental autoimmune encephalomyelitis; Alzheimer's disease; stroke; and more recently in CNS infection caused by Herpes simplex virus, murine hepatitis virus, Theiler's murine encephalomyelitis virus, Japanese encephalitis virus and West Nile virus. Competitive and non-competitive glutamate receptor antagonists promote survival during neurovirulent Sindbis virus encephalitis [35, 36] and improved outcomes during coronavirus encephalitis [37] ↑ neuronal damage/ death ↑ production of NO/ ROS Reviewed in [38] BBB blood brain barrier; CNS central nervous system; HSV herpes simplex virus; MDP macrophage/dendritic cell precursor; MHV murine hepatitis virus; MMP matrix metalloproteinases; NO nitric oxide; NOS2 nitric oxide synthase-2; ROS reactive oxygen species; TMEV Theiler's murine encephalomyelitis virus; WNV West Nile virus. cache = ./cache/cord-299967-90aknp7c.txt txt = ./txt/cord-299967-90aknp7c.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-349285-zmp7sw5q author = Koh, Kyung‐Nam title = Clinical features, genetics, and outcome of pediatric patients with hemophagocytic lymphohistiocytosis in Korea: report of a nationwide survey from Korea Histiocytosis Working Party date = 2014-07-03 pages = extension = .txt mime = text/plain words = 3939 sentences = 220 flesch = 43 summary = BACKGROUND: We analyzed a nationwide registry of pediatric patients with hemophagocytic lymphohistiocytosis (HLH) in Korea to assess the clinical and genetic features and treatment outcomes in pediatric HLH. CONCLUSION: Our study showed the unique predominance of a UNC13D mutation and vulnerability to Epstein–Barr virus infection in Korean children with HLH and emphasizes the prognostic significance of age, liver dysfunction, and treatment responses in this disease. The case report form included information on demographic characteristics, clinical, laboratory, and radiological findings at presentation, genetic mutation analysis, type of treatment and responses to treatment, allogeneic hematopoietic stem cell transplantation, and survival outcomes. In the familial HLH group, only a coagulation abnormality was a marginally significant prognostic factor, and CNS involvement and age were not found to be significantly associated with survival outcome. CNS involvement was found to be a significant prognostic factor in our presumed secondary HLH group but was not associated with a poor outcome in the familial group. cache = ./cache/cord-349285-zmp7sw5q.txt txt = ./txt/cord-349285-zmp7sw5q.txt === reduce.pl bib === id = cord-309109-c5hajb6k author = Matthews, A. E. title = Murine hepatitis virus—A model for virus-induced CNS demyelination date = 2002 pages = extension = .txt mime = text/plain words = 6898 sentences = 335 flesch = 50 summary = Although activated , MHV-speci c, CD8 C T cells transferred to infected mice can control viral replication, they are not suf cient to clear infectious virus from oligodendrocytes (Stohlman et al, 1998b) . Clearance of an MHV strain that primarily infects neurons is delayed in the absence of IFN-gamma, suggesting that it may affect viral control in other cell types as well without being absolutely required for clearance (Lane et al, 1997) . The contribution of humoral immunity to viral clearance and persistent infection in the CNS has been investigated using mice de cient in secreted antibodies or B cells Bergmann et al, 2001; Matthews et al, 2001) . These data suggest that T cells play a role in controlling viral titers, even before 5 d.p.i. Beta2-microglobulinde cient mice, which lack CD8 C T cells, have delayed clearance of virus from the liver . cache = ./cache/cord-309109-c5hajb6k.txt txt = ./txt/cord-309109-c5hajb6k.txt === reduce.pl bib === === reduce.pl bib === id = cord-345254-glm2dxhh author = Hwang, Mihyun title = Distinct CD4 T-cell effects on primary versus recall CD8 T-cell responses during viral encephalomyelitis date = 2015-02-13 pages = extension = .txt mime = text/plain words = 7372 sentences = 372 flesch = 54 summary = By contrast, unhelped memory CD8 T cells mounted poor recall responses when transferred into CD4 T-cell-sufficient mice and could not be sustained in the CNS, despite efficient virus control. Donor mice were treated with anti-mouse CD4 or control mAb at day À2 and 0 relative to intraperitoneal immunization for comparative analysis of 'unhelped' versus 'helped' CD8 T cells. As T cells are the primary mediators of JHMV control in the CNS during the first 14 days p.i. 29, 30 the inability of CD4-depleted mice to reduce viral load suggested impaired CD8 T-cell recruitment or function. 15 We therefore examined potential defects in effector functions of brain-derived unhelped virus-specific CD8 T cells by measurement of ex vivo cytolytic activity and IFN-c expression. To generate unhelped or helped donor memory CD8 T cells, Thy-1.1 mice were either treated with anti-CD4 or control mAb before JHMV immunization. cache = ./cache/cord-345254-glm2dxhh.txt txt = ./txt/cord-345254-glm2dxhh.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-338235-vz2d2x18 author = Pinschewer, Daniel D. title = T cells can mediate viral clearance from ependyma but not from brain parenchyma in a major histocompatibility class I- and perforin-independent manner date = 2010-03-30 pages = extension = .txt mime = text/plain words = 7277 sentences = 349 flesch = 45 summary = This indicated that it was indeed the absence of perforin-dependent cytolytic pathways rather than a general impairment of CD8 + T cell Virus clearance from ependyma To gain further insights on how rLCMV/INDG persisted in the CNS of perforin-deficient, TCRb À/À and RAG À/À mice but not in C57BL/6 controls, we performed histological time course analyses of viral antigen and of infiltrating CD8 + T cells. However, C57BL/6 wild-type animals eliminated the virus by Day 8, whereas slowly but steadily increasing numbers of infected cells were found within the CNS parenchyma of perforin-deficient, TCRb À/À and RAG À/À mice on Days 8, 10 Frequencies of NP396-specific CD8 + T cells in blood were determined on Day 8 using MHC class I tetramers. Total viral RNA loads in the brain of perforin-deficient, MHCI À/À , TCRb À/À and RAG À/À mice are similar as determined by quantitative RT-PCR (Fig. 6C) , providing evidence that within the brain parenchyma, adaptive immune pathways other than MHCI-and perforin-dependent T cell clearance do not substantially influence rLCMV/INDG persistence. cache = ./cache/cord-338235-vz2d2x18.txt txt = ./txt/cord-338235-vz2d2x18.txt === reduce.pl bib === === reduce.pl bib === id = cord-325624-6anybxnk author = Ireland, Derek D. C. title = RNase L Mediated Protection from Virus Induced Demyelination date = 2009-10-02 pages = extension = .txt mime = text/plain words = 8082 sentences = 397 flesch = 43 summary = The unique phenotype of infected RL(−/−) mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. RNase L specifically protected the brain stem from sustained infection and prevented spread of virus to microglia/macrophages located in spinal cord grey matter. The increased pathological changes in both brain stem and spinal cord thus correlated with the high mortality rates of RL 2/2 mice starting at day 9 p.i. The inability to directly link increased axonal damage with enhanced neuronal infection remains puzzling and supports dysregulation of oligodendrocyte function and/or neuroprotective functions of microglia as contributing factors to the severe pathological phenotype and clinical outcome. Numerous functions of RNase L, not directly associated with anti-viral activity, may contribute to the increased susceptibility of RL 2/2 mice to MHV-JHM infection. cache = ./cache/cord-325624-6anybxnk.txt txt = ./txt/cord-325624-6anybxnk.txt === reduce.pl bib === id = cord-324530-tac1unnp author = André, Nicole M title = Distinct mutation in the feline coronavirus spike protein cleavage activation site in a cat with feline infectious peritonitis-associated meningoencephalomyelitis date = 2019-06-26 pages = extension = .txt mime = text/plain words = 2925 sentences = 169 flesch = 48 summary = title: Distinct mutation in the feline coronavirus spike protein cleavage activation site in a cat with feline infectious peritonitis-associated meningoencephalomyelitis CASE SUMMARY: This report describes a cat with chronic, progressive, non-painful, non-lateralizing multifocal neurologic clinical signs associated with feline infectious peritonitis (FIP). Molecular analysis of the coronavirus spike protein within the tissues identified a specific, functionally relevant amino acid change (R793M), which was only identified in tissues associated with the central nervous system (ie, brain and spinal cord). RELEVANCE AND NOVEL INFORMATION: This case report describes an early presentation of a cat with primarily neurologic FIP, with molecular characterization of the virus within various tissues. 18 Molecular analysis of the viral spike protein within the tissues identified a specific, functionally relevant amino acid change (R793M), which was only identified in tissues associated with the CNS (ie, brain and spinal cord). This case report describes a young cat with neurologic FIP in which detailed clinical and molecular characterization of the associated FCoV infection was performed. cache = ./cache/cord-324530-tac1unnp.txt txt = ./txt/cord-324530-tac1unnp.txt === reduce.pl bib === === reduce.pl bib === id = cord-304084-ervaxqph author = Chang, Luan-Yin title = Status of Cellular Rather Than Humoral Immunity is Correlated with Clinical Outcome of Enterovirus 71 date = 2006 pages = extension = .txt mime = text/plain words = 4241 sentences = 229 flesch = 48 summary = The median (range) interval between their disease onset and enrollment in this study was not significantly different among the three groups: 1.9 (1.1-2.9) years for the 7 cases with brainstem encephalitis plus pulmonary edema, 2.5 (0.7-5.2) years for 12 cases with CNS involvement, and 2.6 (0.7-2.7) for 11 uncomplicated cases (p ϭ 0.17 with Kruskal-Wallis test). The median (range) age at this immune study was 3.1 (1.7-3.8) years for the 7 cases with brainstem encephalitis plus pulmonary edema, 5.8 (3.5-7.3) years for 12 cases with CNS involvement, and 4.5 (2.0 -8.1) years for 11 uncomplicated cases (p ϭ 0.005 with Kruskal-Wallis test). EV71 cases with pulmonary edema had a significantly lower PHA stimulation index (p ϭ 0.04, measured to compare the percentages of a response over the median level of increase of all the EV71 cases by using likelihood ratio 2 test). cache = ./cache/cord-304084-ervaxqph.txt txt = ./txt/cord-304084-ervaxqph.txt === reduce.pl bib === === reduce.pl bib === id = cord-320617-ucm7wx8b author = B’Krong, Nguyen Thi Thuy Chinh title = Enterovirus serotypes in patients with central nervous system and respiratory infections in Viet Nam 1997–2010 date = 2018-04-12 pages = extension = .txt mime = text/plain words = 3958 sentences = 221 flesch = 51 summary = Here, we typed Enterovirus A-D (EV) from central nervous system (CNS) and respiratory infections in Viet Nam. METHODS: Data and specimens from prospective observational clinical studies conducted between 1997 and 2010 were used. In Viet Nam, since 2005, various serotypes of EV A, most commonly enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), CV-A10, and CV-A6 have been associated with outbreaks of HFMD [12, 13] and EVs have also been frequently detected in aetiological studies of CNS and respiratory infections [14] [15] [16] [17] [18] . Here we report the clinical associations and serotyping results of EVs that were previously detected in our studies of CNS and respiratory infections in southern and central Viet Nam between 1997 and 2010. Our study illustrates the circulation of diverse enterovirus serotypes belonging to four species (A-D), and their association with respiratory and CNS infections in Viet Nam. These data are important for patient management, laboratory diagnostics and future outbreak response. cache = ./cache/cord-320617-ucm7wx8b.txt txt = ./txt/cord-320617-ucm7wx8b.txt === reduce.pl bib === id = cord-329750-purunxce author = Waldman, Amy title = Childhood multiple sclerosis: A review date = 2006-06-28 pages = extension = .txt mime = text/plain words = 8430 sentences = 481 flesch = 49 summary = Although children and adults with MS have similar neurological symptoms, laboratory (cerebrospinal fluid) data, and neuroimaging findings, the clinical course, pathogenesis, and treatment of childhood onset MS require further investigation. The study concluded that children and adults with MS have similar clinical profiles, including mode of onset, symptoms, and physical and laboratory (cerebral spinal fluid [CSF]) findings. The results from the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) and Safety and Efficacy of Natalizumab in Combination with Interferon ␤-1a in Patients with Relapsing Remitting Multiple Sclerosis (SENTINEL) studies in adult patients indicate that the annualized rate of clinical relapses was reduced by 68%, the number of new and enhancing MRI lesions was reduced by 83%, and a decrease occurred in progression and prolongation of the interval before neurological deterioration, demonstrating the usefulness of the drug [Polman et al., 2006; Rudicket al., 2006] . cache = ./cache/cord-329750-purunxce.txt txt = ./txt/cord-329750-purunxce.txt === reduce.pl bib === id = cord-346339-y7z1sa8y author = Baumgärtner, Wolfgang title = Re-emergence of neuroinfectiology date = 2016-01-11 pages = extension = .txt mime = text/plain words = 1749 sentences = 87 flesch = 33 summary = Neuroinfectiology represents an emerging multidisciplinary field which centers on the complex interactions between CNS and pathogen-associated cellular and molecular processes, inflammation, immune responses, degeneration, stem cell homeostasis as well as tissue repair and regeneration. New molecular detection systems will improve our ability to rapidly diagnose and recognize emerging and re-emerging pathogens and the host genetic factors involved in disease susceptibility, but the development of new strategies for diagnosis, prevention and treatment of neurological disorders will only be efficiently addressed by an interdisciplinary approach bridging the fields of neuroscience and infection medicine. Future studies in neuroinfectiology will address questions relating to the mechanisms of direct and indirect as well as acute, delayed and long-term damage, the role of misdirected immune responses in lesion initiation and the progression as well as prevention of CNS infection by developing appropriate intervention strategies and potential beneficial approaches for tissue regeneration. cache = ./cache/cord-346339-y7z1sa8y.txt txt = ./txt/cord-346339-y7z1sa8y.txt === reduce.pl bib === id = cord-334499-fz7vrnb1 author = Templeton, Steven P. title = Pathogenesis of acute and chronic central nervous system infection with variants of mouse hepatitis virus, strain JHM date = 2007-06-01 pages = extension = .txt mime = text/plain words = 6288 sentences = 297 flesch = 37 summary = Infection of mice with variants of mouse hepatitis virus, strain JHM (MHV-JHM), provide models of acute and chronic viral infection of the central nervous system (CNS). Partially protective anti-viral immune responses may result in persistent infection and chronic demyelinating disease characterized by myelin removal from axons of the CNS and associated with dense macrophage/microglial infiltration. Demyelinating disease during MHV-JHM infection is immune-mediated, as mice that lack T lymphocytes fail to develop disease despite succumbing to encephalitis with high levels of infectious virus in the CNS. Demyelinating disease induced during MHV-JHM infection is partly immune mediated, as mice lacking the ability to generate T cell responses fail to develop demyelination, despite high viral loads and widespread inflammation in the CNS of infected mice [19, 20] . Further studies involve introduction of other chemoattractants into recombinant MHV-JHM, to evaluate their role in demyelinating disease, cell recruitment, generation of immune responses, and clearance of infectious virus in MHV-JHM-infected mice. cache = ./cache/cord-334499-fz7vrnb1.txt txt = ./txt/cord-334499-fz7vrnb1.txt === reduce.pl bib === id = cord-324619-y7gilopu author = Alam, S.B. title = Severe acute respiratory syndrome coronavirus‐2 may be an underappreciated pathogen of the central nervous system date = 2020-07-15 pages = extension = .txt mime = text/plain words = 5244 sentences = 254 flesch = 42 summary = In this review, we examine some of the most recent data of COVID-19-associated neurological disease and the possibility that SARS-CoV-2 may be infecting the CNS. suggested that since SARS-CoV-2 shared significant similarities to severe acute respiratory syndrome coronavirus (SARS-CoV), it was entirely possible that SARS-CoV-2 could similarly penetrate the brain and CNS of infected patients through synapses in the medullary cardiorespiratory center and thereby cause respiratory failure (5) . Similar to these neurotropic HCoVs, SARS-CoV-2 infection in the lungs of some COVID-19 patients may also lead to entry into the CNS and this could occur via two main pathways: i) infection of peripheral nerves and retrograde axonal transport; and/or ii) hematogenous spread and infection of the cells of the blood-brain barrier. In this review, we have extrapolated information from other neurotropic viruses to make some predictions and it is clear that SARS-CoV-2 has the potential to infect the CNS and cause long-term neurologic damage in COVID-19 patients. cache = ./cache/cord-324619-y7gilopu.txt txt = ./txt/cord-324619-y7gilopu.txt === reduce.pl bib === id = cord-333186-gxs74wit author = Ashhurst, Thomas Myles title = The plasticity of inflammatory monocyte responses to the inflamed central nervous system date = 2014-10-31 pages = extension = .txt mime = text/plain words = 8527 sentences = 388 flesch = 37 summary = Viral encephalitis and multiple sclerosis are examples of important human diseases in which the pathogenic contribution of monocytes recruited from the bone marrow plays a critical role in the clinical expression of disease, as they differentiate into macrophage or dendritic cells in the CNS to carry out effector functions. Here we review the current understanding of factors facilitating inflammatory monocyte generation, migration and entry into the brain, as well as their differentiation towards macrophages or dendritic cells in viral and autoimmune disease in relation to their respective disease outcomes. It is also possible that whilst type I IFN (IFN-a/b) and type II IFN (IFN-c) are involved in both CNS diseases, the innate differential production of IFN-a/b, crucial for virus control in the early response against CNS viruses [25] , by a variety of cell types during infection [26] may induce monocyte mobilisation differently from that seen in MS/EAE. cache = ./cache/cord-333186-gxs74wit.txt txt = ./txt/cord-333186-gxs74wit.txt === reduce.pl bib === id = cord-351398-ftkrd1tj author = Stohlman, Stephen A. title = Viral Induced Demyelination date = 2006-04-05 pages = extension = .txt mime = text/plain words = 8223 sentences = 374 flesch = 36 summary = This suggests that demyelination induced by viral infections can result from: 1) a direct viral infection of oligodendroglia resulting in cell death with degeneration of myelin and its subsequent removal; 2) a persistent viral infection, in the presence or absence of infectious virus, resulting in the loss of normal cellular homeostasis and subsequent oligodendroglial death; 3) a vigorous virus‐specific inflammatory response wherein the virus replicates in a cell type other than oligodendroglia, but cytokines and other immune mediators directly damage the oligodendroglia or the myelin sheath; or 4) infection initiates activation of an immune response specific for either oligodendroglia or myelin components. Although the relevance of these neuroantigen specific T cells to the progression of chronic demyelination is still not clear, the data clearly demonstrate activation of immunity to host antigens during inflammation induced by a persistent viral infection. cache = ./cache/cord-351398-ftkrd1tj.txt txt = ./txt/cord-351398-ftkrd1tj.txt === reduce.pl bib === === reduce.pl bib === id = cord-334577-wb6zhovi author = Mangale, Vrushali title = Microglia influence host defense, disease, and repair following murine coronavirus infection of the central nervous system date = 2020-05-25 pages = extension = .txt mime = text/plain words = 5118 sentences = 245 flesch = 43 summary = Treatment with PLX5622, an inhibitor of colony stimulating factor 1 receptor (CSF1R) that efficiently depletes microglia, prior to infection of the central nervous system (CNS) with the neurotropic JHM strain of mouse hepatitis virus (JHMV) resulted in increased mortality compared with control mice that correlated with impaired control of viral replication. tor 1 receptor (CSF1R) that efficiently depletes microglia, prior to infection of the central nervous system (CNS) with the neurotropic JHM strain of mouse hepatitis virus (JHMV) resulted in increased mortality compared with control mice that correlated with impaired control of viral replication. Our findings emphasize an important role for microglia in aiding in host defense in response to JHMV infection of the CNS as well as influencing both the severity of spinal cord demyelination and remyelination in a model of murine coronavirus-induced neurologic disease. cache = ./cache/cord-334577-wb6zhovi.txt txt = ./txt/cord-334577-wb6zhovi.txt === reduce.pl bib === id = cord-353298-vr5hnzp8 author = nan title = In vitro analysis of the oligodendrocyte lineage in mice during demyelination and remyelination date = 1990-09-01 pages = extension = .txt mime = text/plain words = 6929 sentences = 326 flesch = 45 summary = Cultures from demyelinated tissue differed in several ways from those of age-matched controls: first, the total number of O-2A lineage cells was strikingly increased; second, the O-2A population consisted of a higher proportion of O4-positive astrocytes and cells of mixed oligodendrocyte-astrocyte phenotype; and third, all the cell types within the O-2A lineage showed enhanced proliferation. Cultures from demyelinated tissue differed in several ways from those of agematched controls: first, the total number of O-2A lin-cage cells was strikingly increased; second, the O-2A population consisted of a higher proportion of 04positive astrocytes and cells of mixed oligodendrocyteastrocyte phenotype; and third, all the cell types within the O-2A lineage showed enhanced proliferation. Since PDGF, IGF-I, and bFGF can each induce proliferation of neonatal O-2A progenitor cells in the developing rat CNS (reviewed in Dubois-Dalcq and Armstrong, 1990), we assayed the mitogenic effect of these growth factors in our cultures of adult mouse spinal cord (see protocol outlined in Fig. 1 C) . cache = ./cache/cord-353298-vr5hnzp8.txt txt = ./txt/cord-353298-vr5hnzp8.txt === reduce.pl bib === id = cord-331268-kzy33hdb author = Lynch, Sharon G. title = Multiple sclerosis date = 1996-01-31 pages = extension = .txt mime = text/plain words = 13844 sentences = 885 flesch = 47 summary = Abnormalities in the cerebral hemispheres are frequently periventricular in distribution and only occasionally correlate with specific symptoms or signs.6,7 The accumulation of lesions in the frontal lobes is associated with a decline in memory.8 In addition, a change in the number of lesions on cranial MR images correlates with a change in overall clinical status as measured with standard scales.g Observations made with MRI are having a marked impact on both our basic knowledge of MS and on therapeutic trialsJo MRI studies will provide considerable insight into the natural history of the disease and will be an excellent independent variable in future clinical trials. Signs and symptoms that commonly occur as MS progresses include vertigo, tremor, incoordination, increasing spasticity, depression, mood swings, cognitive abnormalities, impotence or other sexual dysfunction, weakness, Lhermitte's sign, gait abnormalities, constipation, urinary incontinence, optic nerve pallor, fatigue, quadriparesis, dysarthria, loss of upper extremity coordination, and dysesthetic pain (Table 1) . cache = ./cache/cord-331268-kzy33hdb.txt txt = ./txt/cord-331268-kzy33hdb.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-355413-ls2nud43 author = Shi, Fu-Dong title = Nature killer cells in the central nervous system date = 2010-01-29 pages = extension = .txt mime = text/plain words = 6858 sentences = 345 flesch = 45 summary = The pathogenic mechanism observed appeared to represent a novel type of autoimmune reaction: an exogenously/chemically induced alteration in a specific subset of cells that was suggested to target them for direct NK cell-mediated killing. The migration of NK cells to the CNS during inflammatory responses and lack of inhibitory signal MHC class I expression within the CNS invites prediction that direct cytolytic effects of NK cells contribute to oligodendrocyte damage and demyelination to CNS diseases such as MS. Intracerebral infection of RAG1 / mice with a recombinant CXCL10-expressing murine coronavirus (MHV) resulted in protection from disease and increased survival that correlated with a significant increase in recruitment and activation of NK cells within the CNS (Walsh et al., 2007) . Associated with decreased resistance to viral infection, CCR5 / mice yielded significantly more virus and expressed higher levels of tumour necrosis factor alpha (TNF-), CXCL1, CCL2, CCL3 and CCL5 in the vagina, spinal cord, and/or brain stem than did wild-type mice. cache = ./cache/cord-355413-ls2nud43.txt txt = ./txt/cord-355413-ls2nud43.txt === reduce.pl bib === id = cord-330553-sukrjl22 author = Stonedahl, Sarah title = The Role of Microglia during West Nile Virus Infection of the Central Nervous System date = 2020-08-28 pages = extension = .txt mime = text/plain words = 5545 sentences = 283 flesch = 41 summary = WNV infection also induces neuroinflammation characterized by activation of innate immune cells, including microglia and astrocytes, production of inflammatory cytokines, breakdown of the blood-brain barrier, and infiltration of peripheral leukocytes. In this review, we will discuss the role of microglia in WNV-induced CNS disease as a contributor both to the protective innate immune response and to the development of long-term neurological damage. Inhibition of these chemokines/cytokines following treatment with minocycline resulted in decreased neuronal cell death following WNV infection of ex vivo spinal cord slice cultures [42] , suggesting they contribute to disease; however, depletion of microglia did not significantly change chemokine/cytokine expression in the brains of WNV-infected mice [60] so it is unclear what role microglia play in the production of these proteins. Death Receptor-Mediated Apoptotic Signaling Is Activated in the Brain following Infection with West Nile Virus in the Absence of a Peripheral Immune Response cache = ./cache/cord-330553-sukrjl22.txt txt = ./txt/cord-330553-sukrjl22.txt === reduce.pl bib === id = cord-342204-9tgxijvn author = Nuzzo, Domenico title = Potential neurological effects of severe COVID-19 infection date = 2020-07-03 pages = extension = .txt mime = text/plain words = 3227 sentences = 183 flesch = 44 summary = In this axis, virus-induced inflammation and oxidative stress could be the common mechanisms responsible for CoV neurological symptoms. People with COVID-19 generally develop respiratory symptoms but the increasing evidence shows that some patients with a severe infection also develop neurological ailments like confusion, stroke, seizure, or loss of smell and taste. Recent studies discussed the neuroinvasive potential of SARS-CoV-2; in fact, some infected subjects did show neurological effects. In fact, detection of some RNA of human-coronavirus in human brain samples clearly demonstrates that these respiratory pathogens are naturally neuroinvasive in J o u r n a l P r e -p r o o f humans and suggests that they establish a persistent infection in human CNS (Arbour et al., 2000) . Therefore, inflammation and oxidative stress systemic, induced by SARS-CoV-2 lung injury, could has effect in CNS causing neuronal dysfunction. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients cache = ./cache/cord-342204-9tgxijvn.txt txt = ./txt/cord-342204-9tgxijvn.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-348746-yaf61cmx author = Foley, Janet E. title = A Review of Coronavirus Infection in the Central Nervous System of Cats and Mice date = 2008-06-28 pages = extension = .txt mime = text/plain words = 5478 sentences = 323 flesch = 37 summary = F eline infectious peritonitis (FIP) is a fatal, immune-mediated disease produced as a result of infection of macrophages by mutant feline coronavirus strains (FIPVs). In acute MHV-A59 infection in CD8ϩ T-cell deficient mice, periventricular encephalitis occurs with lymphocytic infiltration into the choroid plexus, ependyma, and subependymal brain tissue. Depending on mouse strain and immunological status, MHV-JHM produces meningeal inflammation associated with T-cells and macrophages and demyelination but relatively little disease in axons. If mice are pretreated with passive infusions of antibodies or T-cells or if they receive neuroattenuated MHV strains, they develop chronic, but not fatal, disease after MHV-JHM infection. 62, 63 Immunocompetent C57BL/6 mice clear MHV-JHM virus from the brain but develop severe immune-mediated demyelination and paralysis. Two related strains of feline infectious peritonitis virus isolated from immunocompromised cats infected with a feline enteric coronavirus cache = ./cache/cord-348746-yaf61cmx.txt txt = ./txt/cord-348746-yaf61cmx.txt === reduce.pl bib === id = cord-353812-4oxbczqe author = Zoghi, Anahita title = A case of possible atypical demyelinating event of the central nervous system following COVID-19 date = 2020-06-24 pages = extension = .txt mime = text/plain words = 1543 sentences = 99 flesch = 47 summary = Some COVID-19 patients, especially those suffering from a severe disease, are highly likely to have central nervous system (CNS) manifestations. It has been shown that severe infection with SARS-CoV-2 is associated with neurological manifestations such as headache, epilepsy, cerebrovascular events, and encephalitis (Bohmwald et al. Studies on SARS-CoV-1 revealed a delayed self-reactive T-cell suppression due to viral replication, which leads to neuroinflammation, demyelination or axonal damage of the CNS (Savarin et al., 2017 . Recent studies have shown that the novel coronavirus appears to cross the blood-brain barrier and cause acute or delayed CNS demyelination or axonal damage (Desforges et al., 2020) . Moreover, a recent report revealed that CNS delayed demyelinating events following COVID-19 . Severe COVID-19 may affect the CNS and have various acute or delayed neurological complications. During the COVID-19 pandemic, it is important to consider SARS-CoV-2 infection when seeing patients with neurological manifestations, especially those needing immune-modulator therapy, since the established recommendations are insufficient at this time. cache = ./cache/cord-353812-4oxbczqe.txt txt = ./txt/cord-353812-4oxbczqe.txt === reduce.pl bib === === reduce.pl bib === id = cord-026031-hnf5vayd author = Ford, Richard B. title = Emergency Care date = 2009-05-21 pages = extension = .txt mime = text/plain words = 112343 sentences = 6645 flesch = 44 summary = Fresh whole blood Coagulopathy with active hemorrhage (disseminated intravascular coagulation, thrombocytopenia; massive acute hemorrhage; no stored blood available) Stored whole blood Massive acute or ongoing hemorrhage; hypovolemic shock caused by hemorrhage that is unresponsive to conventional crystalloid and colloid fluid therapy; unavailability of equipment required to prepare blood components Packed red blood cells Nonregenerative anemia, immune-mediated hemolytic anemia, correction of anemia before surgery, acute or chronic blood loss Fresh frozen plasma Factor depletion associated with active hemorrhage (congenital: von Willebrand's factor, hemophilia A, hemophilia B; acquired: vitamin K antagonist, rodenticide intoxication, DIC); acute or chronic hypoproteinemia (burns, wound exudates, body cavity effusion; hepatic, renal, or gastrointestinal loss); colostrum replacement in neonates Frozen plasma Acute plasma or protein loss; chronic hypoproteinemia; (contains stable colostrum replacement in neonates; hemophilia B and clotting factors) selected clotting factor deficiencies Platelet-rich plasma* Thrombocytopenia with active hemorrhage (immune-mediated thrombocytopenia, DIC); platelet function abnormality (congenital: thrombasthenia in Bassett hounds; acquired: NSAIDs, other drugs) Cryoprecipitate cache = ./cache/cord-026031-hnf5vayd.txt txt = ./txt/cord-026031-hnf5vayd.txt === reduce.pl bib === id = cord-308201-lavcsqov author = Desforges, Marc title = Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System? date = 2019-12-20 pages = extension = .txt mime = text/plain words = 8470 sentences = 473 flesch = 36 summary = Viruses infecting human CNS cells could then cause different types of encephalopathy, including encephalitis, and long-term neurological diseases. Even though no clear cause and effect link has ever been made with the onset of human neurological diseases, their neuropathogenicity is being increasingly recognized in humans, as several recent reports associated cases of encephalitis [244] , acute flaccid paralysis [271] and other neurological symptoms, including possible complications of HCoV infection such as Guillain-Barré syndrome or ADEM [249, [272] [273] [274] [275] [276] [277] [278] [279] . Like for several other respiratory viruses, accumulating evidence now indicate that HCoV are neuroinvasive in humans and we hypothesize that these recognized respiratory pathogens are potentially neurovirulent as well, as they could participate in short-and long-term neurological disorders either as a result of inadequate host immune responses and/or viral propagation in the CNS, which directly induces damage to resident cells. cache = ./cache/cord-308201-lavcsqov.txt txt = ./txt/cord-308201-lavcsqov.txt === reduce.pl bib === id = cord-257167-rz4r5sj7 author = nan title = Abstracts for the 29th Annual Meeting of the Japan Neuroscience Society (Neuroscience2006) date = 2006-12-31 pages = extension = .txt mime = text/plain words = 240925 sentences = 13617 flesch = 47 summary = SY1-3-11-3 SAD: A novel kinase implicated in phosphoproteome at the presynaptic active zone Toshihisa Ohtsuka Department of Clinical and Molecular Pathology, Faculty of Medicine/Graduate School of Medicine, University of Toyama, Toyama, Japan SAD is a serine/threonine kianse, which has been shown to regulate various neuronal functions during development, including clustering synaptic vesicles, maturation of synapses, and axon/dendrite polarization: these have recently been revealed by genetic studies in C. The results suggest that EAAT4 plays a major role in regulating the concentration of CF transmitters, possibly glutamate, in the route of its extrasynaptic diffusion, and determining the degree of CF-induced inhibition of GABA release from BCs depending on the regional difference of EAAT4 expression in postsynaptic PCs. Chitoshi Takayama 1 , Yoshiro Inoue 1 1 Department of Molecular Neuroanatomy, Hokkaido University School of Medicine, Sapporo, Japan GABA mediates inhibitory transmission in the adult central nervous system (CNS). cache = ./cache/cord-257167-rz4r5sj7.txt txt = ./txt/cord-257167-rz4r5sj7.txt === reduce.pl bib === id = cord-009997-oecpqf1j author = nan title = 2018 ASPHO ABSTRACTS date = 2018-03-31 pages = extension = .txt mime = text/plain words = 182060 sentences = 10342 flesch = 48 summary = Completed cranial radiation and proceeded to allogeneic stem cell transplant with unrelated cord marrow donor and is disease free at approximately day +200.Case 2: 5 year-old female diagnosed with FLT3 and MLL negative AML and completed treatment per COG AAML1031 study on the low risk arm without Bortezomib. Design/Method: This study was a retrospective chart review that included patients 3 to 23 years old with sickle cell disease type SS and S 0 followed at St. Christopher's Hospital for Children. Background: Hydroxyurea, chronic blood transfusion, and bone marrow transplantation can reduce complications, and improve survival in sickle cell disease (SCD), but are associated with a significant decisional dilemma because of the inherent risk-benefit tradeoffs, and the lack of comparative studies. Brown University -Hasbro Children's Hospital, Providence, Rhode Island, United States Background: Despite clinical advances in the treatment of sickle cell disease (SCD) in pediatric and young adult patients, pain remains a significant source of disease-related morbidity. cache = ./cache/cord-009997-oecpqf1j.txt txt = ./txt/cord-009997-oecpqf1j.txt === reduce.pl bib === id = cord-023026-2r84ndzv author = nan title = Posters date = 2013-06-14 pages = extension = .txt mime = text/plain words = 138458 sentences = 6513 flesch = 40 summary = Thus, this work provides the basis to identify molecular pathways regulated by distinct niche/environmental signals and involved in the heterogeneity of adult OPCs. Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative demyelinating disease of the central nervous system (CNS) characterized by inflammation, which leads to formation of demyelinating areas due to loss of oligodendrocytes, astrogliosis and, finally, axonal degeneration. Taken together, these results demonstrate the important role of miR-200b in modulating the MAPK pathway via c-Jun which in turn affects different aspects of the inflammatory process accompanying microglia activation including cytokine response, NO production, phagocytosis and neuronal cell death. For this purpose, coronal cryostat free-floating sections from the brain of both adult transgenic mice and their corresponding wild-type (Wt) littermates, were processed for the study of astrocytes using GFAP immunohistochemistry and microglia using antibodies against Iba1 and several markers commonly related to the activated phenotype of these microglial cells, such as CD16/32 (Fc receptor), F4/80, CD11b, CD206, CD150 and MHC-II. cache = ./cache/cord-023026-2r84ndzv.txt txt = ./txt/cord-023026-2r84ndzv.txt ===== Reducing email addresses Creating transaction Updating adr table ===== Reducing keywords cord-001332-dp6vzgef cord-001017-4qfhltg4 cord-006824-btcdjmfp cord-002119-kl431ev6 cord-002209-xs6qigg4 cord-016954-l3b6n7ej cord-000725-rafwlw0t cord-005734-14ba78cz cord-002757-upwe0cpj cord-009577-29u7pdpk cord-007603-27m9wz0i cord-005393-rhji4io9 cord-008530-yni0poh9 cord-004911-fbge8tkc cord-010187-ymhcfyxx cord-002021-67ao8chx cord-010016-fs8pjy1z cord-011533-im78xwl8 cord-008523-avkgldnp cord-018042-qt7055fw cord-003738-el0wyu74 cord-018034-gx5c9mk8 cord-017144-k7fqneup cord-008586-5jinvuyn cord-007170-svsfu7fj cord-005146-o3roa7br cord-001396-rpnuauwz cord-017917-7aeh6quc cord-021452-9rukc80y cord-015684-q10sx1dm cord-003199-03c9rx3o cord-021069-v9f9874x cord-017499-51yy7y9n cord-022163-7klzsrpu cord-020770-wpub7krf cord-252389-xrdbmosj cord-267166-ecmayzr6 cord-017958-18nnwoav cord-022756-kdgo4rqb cord-028963-u4iupl1s cord-022395-rk31pwoa cord-017954-vobslprh cord-253201-r6vsa0pw cord-104265-kcygxo7h cord-022594-fx044gcd cord-021500-sy6lnt7b cord-252569-9rv1p3qh cord-264794-bgygebgx cord-274315-08mk8a86 cord-253797-a9lmfaho cord-297325-fbilhauu cord-270458-7imgvale cord-270084-xs0pbcip cord-266078-h53zpjab cord-021772-5v4gor2v cord-022659-chwk2bs4 cord-023143-fcno330z cord-276587-ynionj5r cord-270780-3g381rzr cord-276533-cxyndepl cord-268341-103xf3dw cord-271176-wdc4p4bc cord-266441-sd117tzs cord-262281-56tbrl8a cord-278684-txlvla0j cord-268835-catuja6c cord-271396-bol1zpji cord-030371-wp6xmaqe cord-271011-5stsx5je cord-283850-kt8n6pg2 cord-015352-2d02eq3y cord-302796-zi3p2k1b cord-259347-3acsko74 cord-303741-1ou0cy5k cord-280987-uhxk5b1b cord-262786-otxpc46a cord-285493-eg2ltip6 cord-297448-aiorjsyh cord-272981-8gahvdt0 cord-269861-r07osd0w cord-299051-5r2s8z1a cord-298847-szezd2vb cord-294812-nnlzwaf1 cord-292255-zafnq8gl cord-288111-0ufc54kw cord-277679-sc9hugxr cord-284038-93s3ffoy cord-295041-5vpawtef cord-275795-ee7qyw5h cord-311908-sgdq6j6x cord-299949-kmn53e2z cord-317651-lsca8vt2 cord-315656-asvf4roo cord-311845-wnk7itha cord-290566-tmsocyfc cord-299967-90aknp7c cord-312064-hza70mur cord-349285-zmp7sw5q cord-309109-c5hajb6k cord-320909-p93gxjm2 cord-345254-glm2dxhh cord-311847-2czqs84q cord-328763-hcbs20a0 cord-338235-vz2d2x18 cord-329527-0rlotyz3 cord-325624-6anybxnk cord-304084-ervaxqph cord-324530-tac1unnp cord-349135-it5ahzj3 cord-316227-dgyxbgvg cord-320617-ucm7wx8b cord-329750-purunxce cord-346339-y7z1sa8y cord-334499-fz7vrnb1 cord-324619-y7gilopu cord-333186-gxs74wit cord-351398-ftkrd1tj cord-334577-wb6zhovi cord-337365-hugenn14 cord-330553-sukrjl22 cord-353298-vr5hnzp8 cord-331268-kzy33hdb cord-322728-10m3xscs cord-345339-kyboibtq cord-348746-yaf61cmx cord-355413-ls2nud43 cord-342204-9tgxijvn cord-353242-9vy8k6du cord-353812-4oxbczqe cord-023026-2r84ndzv cord-340008-2efzyki4 cord-009997-oecpqf1j cord-257167-rz4r5sj7 cord-332109-ont0tqpn cord-026031-hnf5vayd cord-308201-lavcsqov Creating transaction Updating wrd table ===== Reducing urls cord-001017-4qfhltg4 cord-003738-el0wyu74 cord-020770-wpub7krf cord-267166-ecmayzr6 cord-253201-r6vsa0pw cord-030371-wp6xmaqe cord-262786-otxpc46a cord-320909-p93gxjm2 cord-324530-tac1unnp cord-324619-y7gilopu cord-320617-ucm7wx8b cord-334577-wb6zhovi cord-308201-lavcsqov cord-009997-oecpqf1j cord-353242-9vy8k6du cord-257167-rz4r5sj7 Creating transaction Updating url table ===== Reducing named entities cord-001332-dp6vzgef cord-001017-4qfhltg4 cord-006824-btcdjmfp cord-002209-xs6qigg4 cord-000725-rafwlw0t cord-016954-l3b6n7ej cord-002119-kl431ev6 cord-005734-14ba78cz cord-009577-29u7pdpk cord-007603-27m9wz0i cord-002757-upwe0cpj cord-004911-fbge8tkc cord-005393-rhji4io9 cord-008530-yni0poh9 cord-010187-ymhcfyxx cord-002021-67ao8chx cord-011533-im78xwl8 cord-010016-fs8pjy1z cord-008523-avkgldnp cord-003738-el0wyu74 cord-018042-qt7055fw cord-018034-gx5c9mk8 cord-017144-k7fqneup cord-008586-5jinvuyn cord-007170-svsfu7fj cord-005146-o3roa7br cord-001396-rpnuauwz cord-017917-7aeh6quc cord-021452-9rukc80y cord-015684-q10sx1dm cord-003199-03c9rx3o cord-017499-51yy7y9n cord-021069-v9f9874x cord-020770-wpub7krf cord-022395-rk31pwoa cord-022163-7klzsrpu cord-028963-u4iupl1s cord-017958-18nnwoav cord-252389-xrdbmosj cord-267166-ecmayzr6 cord-017954-vobslprh cord-253201-r6vsa0pw cord-104265-kcygxo7h cord-252569-9rv1p3qh cord-022594-fx044gcd cord-022756-kdgo4rqb cord-264794-bgygebgx cord-021500-sy6lnt7b cord-274315-08mk8a86 cord-253797-a9lmfaho cord-297325-fbilhauu cord-270458-7imgvale cord-270084-xs0pbcip cord-266078-h53zpjab cord-021772-5v4gor2v cord-270780-3g381rzr cord-276533-cxyndepl cord-276587-ynionj5r cord-268341-103xf3dw cord-266441-sd117tzs cord-271176-wdc4p4bc cord-262281-56tbrl8a cord-271396-bol1zpji cord-023143-fcno330z cord-022659-chwk2bs4 cord-271011-5stsx5je cord-030371-wp6xmaqe cord-268835-catuja6c cord-278684-txlvla0j cord-302796-zi3p2k1b cord-259347-3acsko74 cord-283850-kt8n6pg2 cord-303741-1ou0cy5k cord-280987-uhxk5b1b cord-262786-otxpc46a cord-015352-2d02eq3y cord-285493-eg2ltip6 cord-297448-aiorjsyh cord-272981-8gahvdt0 cord-269861-r07osd0w cord-299051-5r2s8z1a cord-298847-szezd2vb cord-277679-sc9hugxr cord-288111-0ufc54kw cord-294812-nnlzwaf1 cord-295041-5vpawtef cord-292255-zafnq8gl cord-284038-93s3ffoy cord-275795-ee7qyw5h cord-311908-sgdq6j6x cord-299949-kmn53e2z cord-317651-lsca8vt2 cord-315656-asvf4roo cord-311845-wnk7itha cord-299967-90aknp7c cord-349285-zmp7sw5q cord-312064-hza70mur cord-309109-c5hajb6k cord-290566-tmsocyfc cord-320909-p93gxjm2 cord-345254-glm2dxhh cord-311847-2czqs84q cord-328763-hcbs20a0 cord-338235-vz2d2x18 cord-329527-0rlotyz3 cord-304084-ervaxqph cord-324530-tac1unnp cord-316227-dgyxbgvg cord-320617-ucm7wx8b cord-329750-purunxce cord-346339-y7z1sa8y cord-334499-fz7vrnb1 cord-325624-6anybxnk cord-324619-y7gilopu cord-333186-gxs74wit cord-351398-ftkrd1tj cord-349135-it5ahzj3 cord-334577-wb6zhovi cord-337365-hugenn14 cord-353298-vr5hnzp8 cord-330553-sukrjl22 cord-331268-kzy33hdb cord-345339-kyboibtq cord-355413-ls2nud43 cord-342204-9tgxijvn cord-353812-4oxbczqe cord-322728-10m3xscs cord-340008-2efzyki4 cord-308201-lavcsqov cord-332109-ont0tqpn cord-348746-yaf61cmx cord-353242-9vy8k6du cord-026031-hnf5vayd cord-023026-2r84ndzv cord-009997-oecpqf1j cord-257167-rz4r5sj7 Creating transaction Updating ent table ===== Reducing parts of speech cord-001332-dp6vzgef cord-001017-4qfhltg4 cord-000725-rafwlw0t cord-002209-xs6qigg4 cord-006824-btcdjmfp cord-016954-l3b6n7ej cord-005734-14ba78cz cord-009577-29u7pdpk cord-007603-27m9wz0i cord-004911-fbge8tkc cord-005393-rhji4io9 cord-002119-kl431ev6 cord-010187-ymhcfyxx cord-010016-fs8pjy1z cord-011533-im78xwl8 cord-018042-qt7055fw cord-017144-k7fqneup cord-008586-5jinvuyn cord-008523-avkgldnp cord-007170-svsfu7fj cord-005146-o3roa7br cord-001396-rpnuauwz cord-017917-7aeh6quc cord-002021-67ao8chx cord-003738-el0wyu74 cord-021452-9rukc80y cord-021069-v9f9874x cord-018034-gx5c9mk8 cord-003199-03c9rx3o cord-252389-xrdbmosj cord-017958-18nnwoav cord-022395-rk31pwoa cord-008530-yni0poh9 cord-267166-ecmayzr6 cord-253201-r6vsa0pw cord-270458-7imgvale cord-022163-7klzsrpu cord-002757-upwe0cpj cord-104265-kcygxo7h cord-017954-vobslprh cord-020770-wpub7krf cord-028963-u4iupl1s cord-252569-9rv1p3qh cord-015684-q10sx1dm cord-264794-bgygebgx cord-253797-a9lmfaho cord-274315-08mk8a86 cord-297325-fbilhauu cord-270084-xs0pbcip cord-266078-h53zpjab cord-270780-3g381rzr cord-276533-cxyndepl cord-276587-ynionj5r cord-268341-103xf3dw cord-271176-wdc4p4bc cord-266441-sd117tzs cord-021500-sy6lnt7b cord-271396-bol1zpji cord-017499-51yy7y9n cord-262281-56tbrl8a cord-302796-zi3p2k1b cord-280987-uhxk5b1b cord-021772-5v4gor2v cord-271011-5stsx5je cord-259347-3acsko74 cord-262786-otxpc46a cord-272981-8gahvdt0 cord-303741-1ou0cy5k cord-268835-catuja6c cord-283850-kt8n6pg2 cord-022594-fx044gcd cord-285493-eg2ltip6 cord-297448-aiorjsyh cord-298847-szezd2vb cord-030371-wp6xmaqe cord-278684-txlvla0j cord-299051-5r2s8z1a cord-288111-0ufc54kw cord-277679-sc9hugxr cord-294812-nnlzwaf1 cord-022756-kdgo4rqb cord-269861-r07osd0w cord-292255-zafnq8gl cord-295041-5vpawtef cord-284038-93s3ffoy cord-311908-sgdq6j6x cord-299949-kmn53e2z cord-317651-lsca8vt2 cord-315656-asvf4roo cord-311845-wnk7itha cord-299967-90aknp7c cord-312064-hza70mur cord-349285-zmp7sw5q cord-309109-c5hajb6k cord-320909-p93gxjm2 cord-345254-glm2dxhh cord-290566-tmsocyfc 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cord-022594-fx044gcd number of items: 136 sum of words: 1,334,511 average size in words: 19,625 average readability score: 43 nouns: cells; patients; cell; mice; virus; disease; infection; brain; expression; response; system; neurons; study; treatment; protein; role; results; studies; blood; cases; microglia; receptor; astrocytes; activity; patient; activation; levels; type; responses; data; analysis; tissue; demyelination; sclerosis; gene; time; days; effects; mouse; lesions; injury; therapy; model; cord; development; function; infections; age; years; myelin verbs: using; shown; induced; include; increased; associated; suggesting; followed; found; causes; expressed; infecting; reported; mediated; compared; develop; occurs; demonstrate; results; observed; indicating; identified; activated; involved; perform; reduced; revealed; leading; treated; required; determine; based; see; presented; described; detect; produced; provides; related; known; decrease; affect; regulating; examined; remain; play; derived; received; controlling; investigated adjectives: viral; clinical; specific; immune; human; multiple; inflammatory; acute; spinal; nervous; central; high; neuronal; severe; respiratory; different; normal; important; present; primary; significant; chronic; neurological; several; peripheral; early; similar; non; common; low; experimental; molecular; positive; anti; first; many; autoimmune; pediatric; higher; functional; glial; possible; cellular; major; neural; dependent; new; long; single; small adverbs: also; however; well; significantly; often; therefore; encephalitis; previously; recently; even; respectively; furthermore; highly; usually; moreover; still; directly; less; especially; later; commonly; approximately; particularly; first; interestingly; mainly; currently; prior; rapidly; specifically; primarily; together; rather; potentially; now; clinically; frequently; typically; generally; predominantly; finally; yet; least; initially; similarly; relatively; alone; early; almost; indeed pronouns: we; it; their; our; its; they; i; them; he; she; his; her; itself; us; you; your; one; themselves; my; me; pdcs; il-4rα; mrnas; himself; rsa59; ourselves; mg; il-1-and; i-; egfp; ␤; tgfis; tgf)-~; tag-1; pdgfar::gfp; p7sngf; p206; na€; n.m.we; ly294002; ivig; interleukin-12; immune/; il1rn; il-23p19; il-1β; il-1b; il-12r2; igg1; ifnar1 proper nouns: CNS; T; MS; Japan; SARS; CD4; CD8; CSF; IFN; Fig; EAE; University; MRI; CoV-2; RNA; COVID-19; mg; MHV; MHC; C; p.i; Tokyo; Univ; II; MBP; CT; Department; kg; TNF; CTL; M; NK; PCR; JHMV; IL-6; JHM; Institute; IV; BDV; mRNA; BBB; GFAP; B; WNV; CoV; PD; School; A; TMEV; Dept keywords: cns; cell; sars; virus; covid-19; disease; patient; infection; csf; ifn; eae; study; mhv; cd8; mbp; cat; mri; mhc; jhmv; il-6; wnv; rna; multiple; gfap; cd4; brain; bbb; usa; tmev; result; protein; pcr; oc43; mouse; microglia; dog; cov-2; child; university; table; schwann; jhm; hlh; fip; expression; case; astrocyte; alzheimer; ace2; west one topic; one dimension: cells file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4060560/ titles(s): ELR(+) chemokine signaling in host defense and disease in a viral model of central nervous system disease three topics; one dimension: patients; cells; virus file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271342/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150038/, https://www.sciencedirect.com/science/article/pii/S1937644818300844 titles(s): Emergency Care | Myelination, Dysmyelination, and Demyelination | T Lymphocytes as Measurable Targets of Protection and Vaccination Against Viral Disorders five topics; three dimensions: patients may patient; cells mice expression; virus infection patients; cells cell mice; cats cells ccr5 file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271342/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150038/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153454/, https://doi.org/10.1016/j.jneumeth.2017.05.011, https://www.ncbi.nlm.nih.gov/pubmed/15771944/ titles(s): Emergency Care | Myelination, Dysmyelination, and Demyelination | Henipaviruses | An optimized method for enumerating CNS derived memory B cells during viral-induced inflammation | Inflammatory cerebrospinal fluid analysis in cats: clinical diagnosis and outcome Type: cord title: keyword-cns-cord date: 2021-05-24 time: 22:41 username: emorgan patron: Eric Morgan email: emorgan@nd.edu input: keywords:cns ==== make-pages.sh htm files ==== make-pages.sh complex files ==== make-pages.sh named enities ==== making bibliographics id: cord-324619-y7gilopu author: Alam, S.B. title: Severe acute respiratory syndrome coronavirus‐2 may be an underappreciated pathogen of the central nervous system date: 2020-07-15 words: 5244.0 sentences: 254.0 pages: flesch: 42.0 cache: ./cache/cord-324619-y7gilopu.txt txt: ./txt/cord-324619-y7gilopu.txt summary: In this review, we examine some of the most recent data of COVID-19-associated neurological disease and the possibility that SARS-CoV-2 may be infecting the CNS. suggested that since SARS-CoV-2 shared significant similarities to severe acute respiratory syndrome coronavirus (SARS-CoV), it was entirely possible that SARS-CoV-2 could similarly penetrate the brain and CNS of infected patients through synapses in the medullary cardiorespiratory center and thereby cause respiratory failure (5) . Similar to these neurotropic HCoVs, SARS-CoV-2 infection in the lungs of some COVID-19 patients may also lead to entry into the CNS and this could occur via two main pathways: i) infection of peripheral nerves and retrograde axonal transport; and/or ii) hematogenous spread and infection of the cells of the blood-brain barrier. In this review, we have extrapolated information from other neurotropic viruses to make some predictions and it is clear that SARS-CoV-2 has the potential to infect the CNS and cause long-term neurologic damage in COVID-19 patients. abstract: Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) causes a highly contagious respiratory disease referred to as COVID‐19. However, emerging evidence indicates that a small, but a growing number of COVID‐19 patients also manifest neurological symptoms, suggesting that SARS‐CoV‐2 may infect the nervous system under some circumstances. SARS‐CoV‐2 primarily enters the body through the epithelial lining of the respiratory and gastrointestinal tracts, but under certain conditions this pleiotropic virus may also infect peripheral nerves and gain entry into the central nervous system (CNS). The brain is shielded by various anatomical and physiological barriers, most notably the blood‐brain barrier (BBB) which functions to prevent harmful substances, including pathogens and pro‐inflammatory mediators, from entering the brain. The BBB is composed of highly specialized endothelial cells, pericytes, mast cells and astrocytes that form the neurovascular unit, which regulates BBB permeability and maintains the integrity of the CNS. In this review, we briefly discuss potential routes of viral entry and the possible mechanisms utilized by SARS‐CoV‐2 to penetrate the CNS, either by disrupting the BBB or infecting the peripheral nerves and using the neuronal network to initiate neuroinflammation. Furthermore, we speculate on the long‐term effects of SARS‐CoV‐2 infection on the brain and in the progression of neurodegenerative diseases known to be associated with other human coronaviruses. Although the mechanisms of SARS‐CoV‐2 entry into the CNS and neurovirulence are currently unknown, the potential pathways described here might pave the way for future research in this area and enable the development of better therapeutic strategies. url: https://doi.org/10.1111/ene.14442 doi: 10.1111/ene.14442 id: cord-266441-sd117tzs author: Almutrafi, Amna title: The Epidemiology of Primary Central Nervous System Tumors at the National Neurologic Institute in Saudi Arabia: A Ten-Year Single-Institution Study date: 2020-02-15 words: 2589.0 sentences: 149.0 pages: flesch: 50.0 cache: ./cache/cord-266441-sd117tzs.txt txt: ./txt/cord-266441-sd117tzs.txt summary: OBJECTIVES: This study is aimed at describing the epidemiological trends of primary CNS tumors in children and adults at the National Neurologic Institute in Saudi Arabia. The worldwide incidence age-standardized rates (ASR) of brain and nervous system cancer in high/very-high HDI (Human Development Index) regions versus low/medium HDI regions was 5.0 and 2.4 for men and 4.0 and 1.7 for women (Saudi Arabia is classified as very-high HDI according to the United Nations Development Program 4-tier system), respectively. Medulloblastomas were the most commonly reported histology type in the pediatric age group followed by low5 Journal of Cancer Epidemiology grade gliomas with a predominance of pilocytic astrocytoma. This study contains the largest institution-based ICD-O and WHO-classified epidemiological analysis of malignant and nonmalignant primary brain tumors in Saudi Arabia in adult and pediatric groups. With regard to a single tumor entity, meningioma was the most common primary brain tumor in adults while in the pediatric age group, medulloblastoma was the leading histology. abstract: OBJECTIVES: This study is aimed at describing the epidemiological trends of primary CNS tumors in children and adults at the National Neurologic Institute in Saudi Arabia. METHODS: A retrospective epidemiological approach was used where data was obtained from the department of pathology registry files and pathology reports. The records of all patients registered from January 2005 to December 2014 with a diagnosis of primary CNS tumor (brain and spinal cord) were selected. Data about sex, age, tumor location, and histologic type were collected. The classification was based on the International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3). RESULTS: Nine hundred and ninety-two (992) cases of primary CNS tumors throughout the ten years (2005 to 2014) were reviewed. There were 714 (71.97%) adults and 278 (28.02%) in the pediatric age group. Nonmalignant tumors dominated the adult population (60.08%) while malignant tumors were more frequent in the pediatric population. Gliomas constituted the most common neoplastic category in children and adults. The most common single tumor entity was meningioma (26.99%, ICD-O-3 histology codes 9530/0, 9539/1, and 9530/3). Medulloblastomas (ICD-O-3 histology codes 9470, 9471, and 9474) were the most common single tumor entity in the pediatric age group (26.62%). CONCLUSIONS: This is an institution-based, detailed, and descriptive epidemiological study of patients with primary CNS tumors in Saudi Arabia. In contrast to other regional and international studies, the medulloblastomas in our institution are more frequent than pilocytic astrocytomas. Limitations to our study included the referral bias and histology-based methodology. url: https://www.ncbi.nlm.nih.gov/pubmed/32256589/ doi: 10.1155/2020/1429615 id: cord-324530-tac1unnp author: André, Nicole M title: Distinct mutation in the feline coronavirus spike protein cleavage activation site in a cat with feline infectious peritonitis-associated meningoencephalomyelitis date: 2019-06-26 words: 2925.0 sentences: 169.0 pages: flesch: 48.0 cache: ./cache/cord-324530-tac1unnp.txt txt: ./txt/cord-324530-tac1unnp.txt summary: title: Distinct mutation in the feline coronavirus spike protein cleavage activation site in a cat with feline infectious peritonitis-associated meningoencephalomyelitis CASE SUMMARY: This report describes a cat with chronic, progressive, non-painful, non-lateralizing multifocal neurologic clinical signs associated with feline infectious peritonitis (FIP). Molecular analysis of the coronavirus spike protein within the tissues identified a specific, functionally relevant amino acid change (R793M), which was only identified in tissues associated with the central nervous system (ie, brain and spinal cord). RELEVANCE AND NOVEL INFORMATION: This case report describes an early presentation of a cat with primarily neurologic FIP, with molecular characterization of the virus within various tissues. 18 Molecular analysis of the viral spike protein within the tissues identified a specific, functionally relevant amino acid change (R793M), which was only identified in tissues associated with the CNS (ie, brain and spinal cord). This case report describes a young cat with neurologic FIP in which detailed clinical and molecular characterization of the associated FCoV infection was performed. abstract: CASE SUMMARY: This report describes a cat with chronic, progressive, non-painful, non-lateralizing multifocal neurologic clinical signs associated with feline infectious peritonitis (FIP). The cat initially presented as underweight, despite a good appetite, and a complete blood count showed non-regenerative anemia. Three months later the cat was returned having developed ataxia and paraparesis, which then progressed over 2 months to tetraparesis, tail plegia, urinary and fecal incontinence, and titubation. Histologic examination of the tissues with subsequent immunohistochemistry confirmed FIP-associated meningoencephalomyelitis following necropsy. Molecular analysis of the coronavirus spike protein within the tissues identified a specific, functionally relevant amino acid change (R793M), which was only identified in tissues associated with the central nervous system (ie, brain and spinal cord). RELEVANCE AND NOVEL INFORMATION: This case report describes an early presentation of a cat with primarily neurologic FIP, with molecular characterization of the virus within various tissues. url: https://doi.org/10.1177/2055116919856103 doi: 10.1177/2055116919856103 id: cord-008530-yni0poh9 author: Asensio, Valerie C. title: Chemokines and viral diseases of the central nervous system date: 2004-01-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: This chapter discusses chemokines and their receptors in the evolution of viral infectious diseases of the central nervous system (CNS). Infection of the human CNS with many different viruses or infection of the rodent CNS induces vigorous host-inflammatory responses with recruitment of large numbers of leukocytes, particularly T lymphocytes and macrophages. Chemokines coordinate trafficking of peripheral blood leukocytes by stimulating their chemotaxis, adhesion, extravasation, and other effector functions. In view of these properties, research efforts have turned increasingly to the possible involvement of chemokines in regulating both peripheral tissue and CNS leukocyte migration during viral infection. The biological effects of chemokines are mediated via their interaction with receptors belonging to the family of seven transmembrane (7TM)-spanning, G-protein coupled receptors (GPCRs). In the normal mammalian CNS, the number of leukocytes present in the brain is scant. However, these cells are attracted to, and accumulate in, a variety of pathologic states, many involving viral infection. Although leukocyte migration into local tissue compartments, such as the CNS, is a multifactorial process, it has become clear that chemokines are pivotal components of this process, providing a necessary chemotactic signal for leukocyte recruitment. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131585/ doi: 10.1016/s0065-3527(01)56006-6 id: cord-333186-gxs74wit author: Ashhurst, Thomas Myles title: The plasticity of inflammatory monocyte responses to the inflamed central nervous system date: 2014-10-31 words: 8527.0 sentences: 388.0 pages: flesch: 37.0 cache: ./cache/cord-333186-gxs74wit.txt txt: ./txt/cord-333186-gxs74wit.txt summary: Viral encephalitis and multiple sclerosis are examples of important human diseases in which the pathogenic contribution of monocytes recruited from the bone marrow plays a critical role in the clinical expression of disease, as they differentiate into macrophage or dendritic cells in the CNS to carry out effector functions. Here we review the current understanding of factors facilitating inflammatory monocyte generation, migration and entry into the brain, as well as their differentiation towards macrophages or dendritic cells in viral and autoimmune disease in relation to their respective disease outcomes. It is also possible that whilst type I IFN (IFN-a/b) and type II IFN (IFN-c) are involved in both CNS diseases, the innate differential production of IFN-a/b, crucial for virus control in the early response against CNS viruses [25] , by a variety of cell types during infection [26] may induce monocyte mobilisation differently from that seen in MS/EAE. abstract: Abstract Over the last three decades it has become increasingly clear that monocytes, originally thought to have fixed, stereotypic responses to foreign stimuli, mediate exquisitely balanced protective and pathogenic roles in disease and immunity. This balance is crucial in core functional organs, such as the central nervous system (CNS), where minor changes in neuronal microenvironments and the production of immune factors can result in significant disease with fatal consequences or permanent neurological sequelae. Viral encephalitis and multiple sclerosis are examples of important human diseases in which the pathogenic contribution of monocytes recruited from the bone marrow plays a critical role in the clinical expression of disease, as they differentiate into macrophage or dendritic cells in the CNS to carry out effector functions. While antigen-specific lymphocyte populations are central to the adaptive immune response in both cases, in viral encephalitis a prominent macrophage infiltration may mediate immunopathological damage, seizure induction, and death. However, the autoimmune response to non-replicating, non-infectious, but abundant, self antigen has a different disease progression, associated with differentiation of significant numbers of infiltrating monocytes into dendritic cells in the CNS. Whilst a predominant presence of macrophages or dendritic cells in the inflamed CNS in viral encephalitis or multiple sclerosis is well described, the way in which the inflamed CNS mobilizes monocytes in the bone marrow to migrate to the CNS and the key drivers that lead to these specific differentiation pathways in vivo are not well understood. Here we review the current understanding of factors facilitating inflammatory monocyte generation, migration and entry into the brain, as well as their differentiation towards macrophages or dendritic cells in viral and autoimmune disease in relation to their respective disease outcomes. url: https://www.ncbi.nlm.nih.gov/pubmed/25086710/ doi: 10.1016/j.cellimm.2014.07.002 id: cord-311908-sgdq6j6x author: Atkins, G. J. title: Transient virus infection and multiple sclerosis date: 2000-09-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Multiple sclerosis (MS) is a chronic, demyelinating disease of the CNS in which autoimmunity to myelin plays a role in pathogenesis. The epidemiology of MS indicates that it may be triggered by a virus infection before the age of adolescence, but attempts to associate a specific virus with MS have produced equivocal results. Many studies of the aetiology of MS have postulated that a persistent virus infection is involved, but transient virus infection may provide a plausible alternative mechanism that could explain many of the inconsistencies in MS research. The most studied animal model of MS is chronic relapsing experimental autoimmune encephalomyelitis (CREAE), which is induced in susceptible animals following injection of myelin components. While CREAE cannot provide information on the initiating factor for MS, it may mimic disease processes occurring after an initial trigger that may involve transient virus infection. The disease process may comprise separate triggering and relapse phases. The triggering phase may involve sensitisation to myelin antigens as a result of damage to oligodendrocytes or molecular mimicry. The relapse phase could be similar to CREAE, or alternatively relapses may be induced by further transient virus infections which may not involve infection of the CNS, but which may involve the recrudescence of anti‐myelin autoimmunity. Although current vaccines have a high degree of biosafety, it is suggested that the measles‐mumps‐rubella vaccine in particular could be modified to obviate any possibility of triggering anti‐myelin autoimmunity. Copyright © 2000 John Wiley & Sons, Ltd. url: https://www.ncbi.nlm.nih.gov/pubmed/11015741/ doi: 10.1002/1099-1654(200009/10)10:5<291::aid-rmv278>3.0.co;2-u id: cord-297448-aiorjsyh author: Atkinson, Jeffrey R. title: Dynamics of Virus-Specific Memory B Cells and Plasmablasts following Viral Infection of the Central Nervous System date: 2019-01-04 words: 7702.0 sentences: 393.0 pages: flesch: 52.0 cache: ./cache/cord-297448-aiorjsyh.txt txt: ./txt/cord-297448-aiorjsyh.txt summary: During infection with a gliatropic mouse hepatitis virus (MHV) derived from the JHM strain (JHMv2.2-1), IgDpositive (IgD ϩ ) (naive/transitional) B cells prevail early, but they decrease coincident with increasing proportions of CD138 ϩ antibody (Ab)-secreting cells (ASC) and CD138 Ϫ IgG ϩ isotype-switched memory B cells (Bmem) as germinal centers (GCs) are formed in draining lymph nodes (1, 2) . To better characterize the proportions of virus-specific Bmem and ASC accumulating in the CLN and the CNS following viral encephalomyelitis, we took advantage of mice expressing tamoxifen-inducible Cre recombinase (Cre-ERT2) under the Aicda promoter crossed with Rosa26-loxP-tdTomato reporter mice to obtain progeny in which AIDexpressing cells can be identified by fluorescence following tamoxifen administration (4, 27) . Comparison of total numbers of tdTomato ϩ cells and their compositions of ASC and Bmem in brains and spinal cords over time following infection revealed overall similar kinetics of virus-specific B cell accumulation (Fig. 5B) . abstract: Humoral responses within the central nervous system (CNS) are common to many neurotropic viral infections, with antibody (Ab)-secreting cells (ASC) contributing to local protection. However, a role for virus-specific memory B cells (Bmem) within the CNS is poorly explored due to lack of robust phenotypic or functional identification in mice. This study takes advantage of the progeny of mice expressing tamoxifen-inducible Cre recombinase (Cre-ERT2) under the Aicda promoter crossed with Rosa26-loxP-tdTomato reporter mice (AID(Cre)-Rosa26(tdTomato)) to monitor B cells having undergone activation-induced cytidine deaminase (AID)-mediated somatic hypermutation (SHM) following neurotropic coronavirus infection. AID detection via tdTomato expression allowed tracking of virus-specific ASC and Bmem in priming and effector sites throughout infection. In draining lymph nodes, tdTomato-positive (tdTomato(+)) ASC were most prevalent prior to germinal center (GC) formation, but total tdTomato(+) B cells only peaked with robust GC formation at day 14 p.i. Moreover, their proportion of Bmem dominated over the proportion of ASC throughout infection. In the CNS, tdTomato(+) cells started emerging at day 14 p.i. While they initially comprised mainly Bmem, the proportions of ASC and Bmem became similar as tdTomato(+) B cells increased throughout viral persistence. Delayed tamoxifen treatment demonstrated ongoing CNS recruitment of tdTomato(+) B cells, mainly ASC, primed late during GC reactions. Overall, the data support the idea that virus-induced B cells exhibiting SHM require peripheral GC formation to emerge in the CNS. Ongoing GC reactions and regional signals further regulate dynamics within the CNS, with preferential maintenance of tdTomato(+) B cells in spinal cords relative to that in brains during viral persistence. IMPORTANCE The prevalence and role of antigen-specific Bmem in the CNS during viral encephalomyelitis is largely undefined. A lack of reliable markers identifying murine Bmem has made it difficult to assess their contribution to local antiviral protection via antigen presentation or conversion to ASC. Using reporter mice infected with neurotropic coronavirus to track virus-specific Bmem and ASC, this report demonstrates that both subsets only emerge in the CNS following peripheral GC formation and subsequently prevail. While early GC reactions supported preferential Bmem accumulation in the CNS, late GC reactions favored ASC accumulation, although Bmem outnumbered ASC in draining lymph nodes throughout infection. Importantly, virus-specific B cells undergoing sustained GC selection were continually recruited to the persistently infected CNS. Elucidating the factors governing temporal events within GCs, as well as regional CNS cues during viral persistence, will aid intervention to modulate CNS humoral responses in the context of infection and associated autoimmune pathologies. url: https://www.ncbi.nlm.nih.gov/pubmed/30333176/ doi: 10.1128/jvi.00875-18 id: cord-346339-y7z1sa8y author: Baumgärtner, Wolfgang title: Re-emergence of neuroinfectiology date: 2016-01-11 words: 1749.0 sentences: 87.0 pages: flesch: 33.0 cache: ./cache/cord-346339-y7z1sa8y.txt txt: ./txt/cord-346339-y7z1sa8y.txt summary: Neuroinfectiology represents an emerging multidisciplinary field which centers on the complex interactions between CNS and pathogen-associated cellular and molecular processes, inflammation, immune responses, degeneration, stem cell homeostasis as well as tissue repair and regeneration. New molecular detection systems will improve our ability to rapidly diagnose and recognize emerging and re-emerging pathogens and the host genetic factors involved in disease susceptibility, but the development of new strategies for diagnosis, prevention and treatment of neurological disorders will only be efficiently addressed by an interdisciplinary approach bridging the fields of neuroscience and infection medicine. Future studies in neuroinfectiology will address questions relating to the mechanisms of direct and indirect as well as acute, delayed and long-term damage, the role of misdirected immune responses in lesion initiation and the progression as well as prevention of CNS infection by developing appropriate intervention strategies and potential beneficial approaches for tissue regeneration. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/26754640/ doi: 10.1007/s00401-016-1535-3 id: cord-020770-wpub7krf author: Benmamar-Badel, Anouk title: Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies date: 2020-04-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Microglial heterogeneity has been the topic of much discussion in the scientific community. Elucidation of their plasticity and adaptability to disease states triggered early efforts to characterize microglial subsets. Over time, their phenotypes, and later on their homeostatic signature, were revealed, through the use of increasingly advanced transcriptomic techniques. Recently, an increasing number of these “microglial signatures” have been reported in various homeostatic and disease contexts. Remarkably, many of these states show similar overlapping microglial gene expression patterns, both in homeostasis and in disease or injury. In this review, we integrate information from these studies, and we propose a unique subset, for which we introduce a core signature, based on our own research and reports from the literature. We describe that this subset is found in development and in normal aging as well as in diverse diseases. We discuss the functions of this subset as well as how it is induced. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147523/ doi: 10.3389/fimmu.2020.00430 id: cord-005734-14ba78cz author: Bennett, Jami L. title: CCL2 transgene expression in the central nervous system directs diffuse infiltration of CD45(high)CD11b(+) monocytes and enhanced Theiler’s murine encephalomyelitis virus-induced demyelinating disease date: 2003 words: 7588.0 sentences: 361.0 pages: flesch: 45.0 cache: ./cache/cord-005734-14ba78cz.txt txt: ./txt/cord-005734-14ba78cz.txt summary: title: CCL2 transgene expression in the central nervous system directs diffuse infiltration of CD45(high)CD11b(+) monocytes and enhanced Theiler''s murine encephalomyelitis virus-induced demyelinating disease To test the hypothesis that the presence of CCL2 in the CNS could regulate an immune-mediated, macrophage-dependent demyelinating disease, we infected either control, JE32, or JE95 (described previously; Huang et al [2002] ) transgenic mice with TMEV and assessed the animals for resulting clinical paralysis. However, it could be possible that the presence of any virus in the CNS of CCL2-transgenic mice would be a sufficient stimulus to activate the accumulated macrophage pool, initiating inflammation and development of demyelinating disease. Further, the mCMV studies demonstrate that the accelerated disease observed in CCL2-transgenic mice is specific to TMEV infection and not due to a nonspecific activation of localized monocytes/macrophages by any virus introduced into the CNS. abstract: CCL2 is a member of the CC chemokine family that mediates the migration and recruitment of monocytes and T cells and has been identified in the central nervous system (CNS) during several neuroinflammatory diseases. In order to examine the biological effect of constitutive CCL2 expression in the CNS, the authors engineered a mouse that expressed CCL2 in the CNS under control of the human glial fibrillary acidic protein (hGFAP) promoter. The results demonstrated that transgenic expression of CCL2 in the CNS resulted in diffuse CNS monocyte infiltration and accumulation. Transgenic CCL2 expression did not alter normal development, differentiation, or function of T cells. There was no evidence of overt CNS disease or other pathologic phenotype when mice were left unchallenged with antigen or uninfected. However, when CCL2 transgenic mice were given a peripheral challenge of lipopolysaccharide (LPS), an inflammatory infiltrate with organized perivascular lesions developed. Infection of the transgenic mice with Theiler’s murine encephalomyelitis virus (TMEV) resulted in accelerated onset and increased severity of clinical and histological disease. These results suggest that CCL2 expression in the CNS is a major pathogenic factor that drives macrophage accumulation in the development of CNS inflammatory disease. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095321/ doi: 10.1080/13550280390247551 id: cord-021452-9rukc80y author: Bergman, Robert L. title: Miscellaneous Spinal Cord Diseases date: 2009-05-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149771/ doi: 10.1016/b0-72-160423-4/50054-8 id: cord-001396-rpnuauwz author: Blanc, Caroline A title: FTY720 (fingolimod) modulates the severity of viral-induced encephalomyelitis and demyelination date: 2014-08-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: FTY720 (fingolimod) is the first oral drug approved by the Food and Drug Administration for treatment of patients with the relapsing-remitting form of the human demyelinating disease multiple sclerosis. Evidence suggests that the therapeutic benefit of FTY720 occurs by preventing the egress of lymphocytes from lymph nodes thereby inhibiting the infiltration of disease-causing lymphocytes into the central nervous system (CNS). We hypothesized that FTY720 treatment would affect lymphocyte migration to the CNS and influence disease severity in a mouse model of viral-induced neurologic disease. METHODS: Mice were infected intracranially with the neurotropic JHM strain of mouse hepatitis virus. Infected animals were treated with increasing doses (1, 3 and 10 mg/kg) of FTY720 and morbidity and mortality recorded. Infiltration of inflammatory virus-specific T cells (tetramer staining) into the CNS of FTY720-treated mice was determined using flow cytometry. The effects of FTY720 treatment on virus-specific T cell proliferation, cytokine production and cytolytic activity were also determined. The severity of neuroinflammation and demyelination in FTY720-treated mice was examined by flow cytometry and histopathologically, respectively, in the spinal cords of the mice. RESULTS: Administration of FTY720 to JHMV-infected mice resulted in increased clinical disease severity and mortality. These results correlated with impaired ability to control viral replication (P < 0.05) within the CNS at days 7 and 14 post-infection, which was associated with diminished accumulation of virus-specific CD4+ and CD8+ T cells (P < 0.05) into the CNS. Reduced neuroinflammation in FTY720-treated mice correlated with increased retention of T lymphocytes within draining cervical lymph nodes (P < 0.05). Treatment with FTY720 did not affect virus-specific T cell proliferation, expression of IFN-γ, TNF-α or cytolytic activity. FTY720-treated mice exhibited a reduction in the severity of demyelination associated with dampened neuroinflammation. CONCLUSION: These findings indicate that FTY720 mutes effective anti-viral immune responses through impacting migration and accumulation of virus-specific T cells within the CNS during acute viral-induced encephalomyelitis. FTY720 treatment reduces the severity of neuroinflammatory-mediated demyelination by restricting the access of disease-causing lymphocytes into the CNS but is not associated with viral recrudescence in this model. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148542/ doi: 10.1186/s12974-014-0138-y id: cord-329527-0rlotyz3 author: Bohmwald, Karen title: Neurologic Alterations Due to Respiratory Virus Infections date: 2018-10-26 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Central Nervous System (CNS) infections are one of the most critical problems in public health, as frequently patients exhibit neurologic sequelae. Usually, CNS pathologies are caused by known neurotropic viruses such as measles virus (MV), herpes virus and human immunodeficiency virus (HIV), among others. However, nowadays respiratory viruses have placed themselves as relevant agents responsible for CNS pathologies. Among these neuropathological viruses are the human respiratory syncytial virus (hRSV), the influenza virus (IV), the coronavirus (CoV) and the human metapneumovirus (hMPV). These viral agents are leading causes of acute respiratory infections every year affecting mainly children under 5 years old and also the elderly. Up to date, several reports have described the association between respiratory viral infections with neurological symptoms. The most frequent clinical manifestations described in these patients are febrile or afebrile seizures, status epilepticus, encephalopathies and encephalitis. All these viruses have been found in cerebrospinal fluid (CSF), which suggests that all these pathogens, once in the lungs, can spread throughout the body and eventually reach the CNS. The current knowledge about the mechanisms and routes used by these neuro-invasive viruses remains scarce. In this review article, we describe the most recent findings associated to neurologic complications, along with data about the possible invasion routes of these viruses in humans and their various effects on the CNS, as studied in animal models. url: https://www.ncbi.nlm.nih.gov/pubmed/30416428/ doi: 10.3389/fncel.2018.00386 id: cord-312064-hza70mur author: Borrow, P title: Investigation of the role of delayed-type-hypersensitivity responses to myelin in the pathogenesis of Theiler's virus-induced demyelinating disease. date: 1998-04-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The contribution of autoimmune responses to the pathogenesis of Theiler's virus-induced demyelinating disease was investigated. Delayed-type hypersensitivity responses to myelin were examined in both symptomatic and asymptomatic mice at different times post-infection, in order to determine whether autoreactivity correlates with the development of demyelination. The results indicate that although autoimmune responses probably do not play a major role in the initiation of demyelination at early times post-infection, autoreactivity to myelin antigens dose eventually develop in symptomatic animals, perhaps through the mechanism of epitope spreading. Autoimmunity to myelin components is therefore an additional factor that may contribute to lesion progression in chronically diseased animals. url: https://www.ncbi.nlm.nih.gov/pubmed/9659218/ doi: nan id: cord-104265-kcygxo7h author: Brabb, Thea title: In Situ Tolerance within the Central Nervous System as a Mechanism for Preventing Autoimmunity date: 2000-09-18 words: 7106.0 sentences: 303.0 pages: flesch: 52.0 cache: ./cache/cord-104265-kcygxo7h.txt txt: ./txt/cord-104265-kcygxo7h.txt summary: Animal models of MS have shown that CNS-specific T cells are present in the peripheral T cell repertoire of healthy mice and cause autoimmune disease only when they are activated by immunization. Strikingly, transgenic T cells isolated from the CNS that are specific for myelin basic protein (MBP) are also primarily phenotypically naive but are unresponsive to antigenic stimulation in vitro. Our data demonstrate that as MBP TCR transgenic mice age, an increasing number of T cells expressing MBP-specific TCRs are activated and converted to a memory phenotype in the absence of spontaneous EAE. In addition, naive CD4 ϩ T cells specific for non-CNS antigens proliferate equally well when they are isolated from either the CNS or LNs, and it is only T cells from MBP TCR transgenic mice that are nonresponsive. Despite tolerance induction of naive MBP-specific CNS T cells, spontaneous EAE still occurs in a percentage of the MBP TCR transgenic mice, primarily within an age window of 5-12 wk (14) . abstract: Multiple sclerosis (MS) is believed to be an autoimmune disease in which autoreactive T cells infiltrate the central nervous system (CNS). Animal models of MS have shown that CNS-specific T cells are present in the peripheral T cell repertoire of healthy mice and cause autoimmune disease only when they are activated by immunization. T cell entry into the CNS is thought to require some form of peripheral activation because the blood–brain barrier prohibits trafficking of this tissue by naive cells. We report here that naive T cells can traffic to the CNS without prior activation. Comparable numbers of T cells are found in the CNS of both healthy recombinase activating gene (Rag)(−/)− T cell receptor (TCR) transgenic mice and nontransgenic mice even when the transgenic TCR is specific for a CNS antigen. Transgenic T cells isolated from the CNS that are specific for non-CNS antigens are phenotypically naive and proliferate robustly to antigenic stimulation in vitro. Strikingly, transgenic T cells isolated from the CNS that are specific for myelin basic protein (MBP) are also primarily phenotypically naive but are unresponsive to antigenic stimulation in vitro. Mononuclear cells from the CNS of MBP TCR transgenic but not nontransgenic mice can suppress the response of peripheral MBP-specific T cells in vitro. These results indicate that naive MBP-specific T cells can traffic to the CNS but do not trigger autoimmunity because they undergo tolerance induction in situ. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193284/ doi: nan id: cord-270780-3g381rzr author: Bradshaw, J. M. title: A Retrospective Study of 286 Cases of Neurological Disorders of the Cat date: 2004-10-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract Archive central nervous tissue from 286 cats with neurological disorders was reviewed for histological evidence of feline spongiform encephalopathy (FSE), which may have occurred before it was first recognized in 1990. The following six categories of disease were identified: congenital; degenerative; inflammatory; neoplastic; FSE; lesion-free. The largest category (inflammatory) contained 92 cats, of which 47 were considered to be consistent with infection by feline infectious peritonitis (FIP) virus. Six cats showed evidence of more than one disease process; thus, one cat with FIP also had toxocara infection of the lateral ventricles and five cats with FSE also showed perivascular cuffing suggestive of concurrent viral infection. In only two cases did the diagnosis on review differ significantly from the original interpretation. There was no evidence of FSE before the original case was recognized in April 1990. url: https://www.sciencedirect.com/science/article/pii/S0021997504000209 doi: 10.1016/j.jcpa.2004.01.010 id: cord-022163-7klzsrpu author: Broder, Christopher C. title: Henipaviruses date: 2016-09-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The first henipaviruses, Hendra virus (HeV), and Nipah virus (NiV) were pathogenic zoonoses that emerged in the mid to late 1990s causing serious disease outbreaks in livestock and humans. HeV was recognized in Australia 1994 in horses exhibiting respiratory disease along with a human case fatality, and then NiV was identified during a large outbreak of human cases of encephalitis with high mortality in Malaysia and Singapore in 1998–1999 along with respiratory disease in pigs which served as amplifying hosts. The recently identified third henipavirus isolate, Cedar virus (CedPV), is not pathogenic in animals susceptible to HeV and NiV disease. Molecular detection of additional henipavirus species has been reported but no additional isolates of virus have been reported. Central pathological features of both HeV and NiV infection in humans and several susceptible animal species is a severe systemic and often fatal neurologic and/or respiratory disease. In people, both viruses can also manifest relapsed encephalitis following recovery from an acute infection, particularly NiV. The recognized natural reservoir hosts of HeV, NiV, and CedPV are pteropid bats, which do not show clinical illness when infected. With spillovers of HeV continuing to occur in Australia and NiV in Bangladesh and India, these henipaviruses continue to be important transboundary biological threats. NiV in particular possesses several features that highlight a pandemic potential, such as its ability to infect humans directly from natural reservoirs or indirectly from other susceptible animals along with a capacity of limited human-to-human transmission. Several henipavirus animal challenge models have been developed which has aided in understanding HeV and NiV pathogenesis as well as how they invade the central nervous system, and successful active and passive immunization strategies against HeV and NiV have been reported which target the viral envelope glycoproteins. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153454/ doi: 10.1007/978-3-319-33133-1_3 id: cord-320617-ucm7wx8b author: B’Krong, Nguyen Thi Thuy Chinh title: Enterovirus serotypes in patients with central nervous system and respiratory infections in Viet Nam 1997–2010 date: 2018-04-12 words: 3958.0 sentences: 221.0 pages: flesch: 51.0 cache: ./cache/cord-320617-ucm7wx8b.txt txt: ./txt/cord-320617-ucm7wx8b.txt summary: Here, we typed Enterovirus A-D (EV) from central nervous system (CNS) and respiratory infections in Viet Nam. METHODS: Data and specimens from prospective observational clinical studies conducted between 1997 and 2010 were used. In Viet Nam, since 2005, various serotypes of EV A, most commonly enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), CV-A10, and CV-A6 have been associated with outbreaks of HFMD [12, 13] and EVs have also been frequently detected in aetiological studies of CNS and respiratory infections [14] [15] [16] [17] [18] . Here we report the clinical associations and serotyping results of EVs that were previously detected in our studies of CNS and respiratory infections in southern and central Viet Nam between 1997 and 2010. Our study illustrates the circulation of diverse enterovirus serotypes belonging to four species (A-D), and their association with respiratory and CNS infections in Viet Nam. These data are important for patient management, laboratory diagnostics and future outbreak response. abstract: BACKGROUND: Enteroviruses are the most common causative agents of human illness. Enteroviruses have been associated with regional and global epidemics, recently, including with severe disease (Enterovirus A71 and D68), and are of interest as emerging viruses. Here, we typed Enterovirus A-D (EV) from central nervous system (CNS) and respiratory infections in Viet Nam. METHODS: Data and specimens from prospective observational clinical studies conducted between 1997 and 2010 were used. Species and serotypes were determined using type-specific RT-PCR and viral protein 1 or 4 (VP1, VP4) sequencing. RESULTS: Samples from patients with CNS infection (51 children – 10 CSF and 41 respiratory/rectal swabs) and 28 adults (28 CSF) and respiratory infection (124 children – 124 respiratory swabs) were analysed. Twenty-six different serotypes of the four Enterovirus species (A-D) were identified, including EV-A71 and EV-D68. Enterovirus B was associated with viral meningitis in children and adults. Hand, foot and mouth disease associated Enteroviruses A (EV-A71 and Coxsackievirus [CV] A10) were detected in children with encephalitis. Diverse serotypes of all four Enterovirus species were found in respiratory samples, including 2 polio-vaccine viruses, but also 8 CV-A24 and 8 EV-D68. With the exception of EV-D68, the relevance of these viruses in respiratory infection remains unknown. CONCLUSION: We describe the diverse spectrum of enteroviruses from patients with CNS and respiratory infections in Viet Nam between 1997 and 2010. These data confirm the global circulation of Enterovirus genera and their associations and are important for clinical diagnostics, patient management, and outbreak response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-0980-0) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pubmed/29650033/ doi: 10.1186/s12985-018-0980-0 id: cord-015684-q10sx1dm author: Cacabelos, Ramón title: Pharmacogenomic Biomarkers in Neuropsychiatry: The Path to Personalized Medicine in Mental Disorders date: 2009 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Neuropsychiatric disorders and dementia represent a major cause of disability and high cost in developed societies. Most disorders of the central nervous system (CNS) share some common features, such as a genomic background in which hundreds of genes might be involved, genome-environment interactions, complex pathogenic pathways, poor therapeutic outcomes, and chronic disability. Recent advances in genomic medicine can contribute to accelerate our understanding on the pathogenesis of CNS disorders, improve diagnostic accuracy with the introduction of novel biomarkers, and personalize therapeutics with the incorporation of pharmacogenetic and pharmacogenomic procedures to drug development and clinical practice. The pharmacological treatment of CNS disorders, in general, accounts for 10–20% of direct costs, and less than 30–40% of the patients are moderate responders to conventional drugs, some of which may cause important adverse drugs reactions (ADRs). Pharmacogenetic and pharmacogenomic factors may account for 60–90% of drug variability in drug disposition and pharmacodynamics. Approximately 60–80% of CNS drugs are metabolized via enzymes of the CYP gene superfamily; 18% of neuroleptics are major substrates of CYP1A2 enzymes, 40% of CYP2D6, and 23% of CYP3A4; 24% of antidepressants are major substrates of CYP1A2 enzymes, 5% of CYP2B6, 38% of CYP2C19, 85% of CYP2D6, and 38% of CYP3A4; 7% of benzodiazepines are major substrates of CYP2C19 enzymes, 20% of CYP2D6, and 95% of CYP3A4. About 10–20% of Caucasians are carriers of defective CYP2D6 polymorphic variants that alter the metabolism of many psychotropic agents. Other 100 genes participate in the efficacy and safety of psychotropic drugs. The incorporation of pharmacogenetic/ pharmacogenomic protocols to CNS research and clinical practice can foster therapeutics optimization by helping to develop cost-effective pharmaceuticals and improving drug efficacy and safety. To achieve this goal several measures have to be taken, including: (a) educate physicians and the public on the use of genetic/ genomic screening in the daily clinical practice; (b) standardize genetic testing for major categories of drugs; (c) validate pharmacogenetic and pharmacogenomic procedures according to drug category and pathology; (d) regulate ethical, social, and economic issues; and (e) incorporate pharmacogenetic and pharmacogenomic procedures to both drugs in development and drugs in the market to optimize therapeutics. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115027/ doi: 10.1007/978-90-481-2298-1_1 id: cord-302796-zi3p2k1b author: Cardona, Astrid E. title: Chemokines in and out of the central nervous system: much more than chemotaxis and inflammation date: 2008-05-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Actions of chemokines and the interaction with specific receptors go beyond their original, defined role of recruiting leukocytes to inflamed tissues. Chemokine receptor expression in peripheral elements and resident cells of the central nervous system (CNS) represents a relevant communication system during neuroinflammatory conditions. The following examples are described in this review: Chemokine receptors play important homeostatic properties by regulating levels of specific ligands in blood and tissues during healthy and pathological conditions; chemokines and their receptors are clearly involved in leukocyte extravasation and recruitment to the CNS, and current studies are directed toward understanding the interaction between chemokine receptors and matrix metalloproteinases in the process of blood brain barrier breakdown. We also propose novel functions of chemokine receptors during demyelination/remyelination, and developmental processes. url: https://www.ncbi.nlm.nih.gov/pubmed/18467654/ doi: 10.1189/jlb.1107763 id: cord-017958-18nnwoav author: Chan, Andrew title: Apoptotic Cell Death in Experimental Autoimmune Encephalomyelitis: Apoptosis of effector cells as a safe mechanism in the termination of an autoimmune inflammatory attack date: 2005 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Particularly in the vulnerable CNS with a low capacity for regeneration specialized mechanisms must be active for the fast and gentle elimination of dysregulated autoaggressive immune cells. In EAE, local apoptosis of autoimmune T-cells has been identified as a safe means for the removal of these unwanted cells. T-cell apoptosis in situ followed by phagocytic clearance of apoptotic remnants by glia assures a minimum of detrimental bystander damage to the local parenchyma and down-regulates the local inflammatory reaction. The pharmacological augmentation of local apoptosis of inflammatory effector cells might gain therapeutic importance also in human neuroimmunological diseases such as multiple sclerosis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122661/ doi: 10.1007/0-387-25518-4_24 id: cord-304084-ervaxqph author: Chang, Luan-Yin title: Status of Cellular Rather Than Humoral Immunity is Correlated with Clinical Outcome of Enterovirus 71 date: 2006 words: 4241.0 sentences: 229.0 pages: flesch: 48.0 cache: ./cache/cord-304084-ervaxqph.txt txt: ./txt/cord-304084-ervaxqph.txt summary: The median (range) interval between their disease onset and enrollment in this study was not significantly different among the three groups: 1.9 (1.1-2.9) years for the 7 cases with brainstem encephalitis plus pulmonary edema, 2.5 (0.7-5.2) years for 12 cases with CNS involvement, and 2.6 (0.7-2.7) for 11 uncomplicated cases (p ϭ 0.17 with Kruskal-Wallis test). The median (range) age at this immune study was 3.1 (1.7-3.8) years for the 7 cases with brainstem encephalitis plus pulmonary edema, 5.8 (3.5-7.3) years for 12 cases with CNS involvement, and 4.5 (2.0 -8.1) years for 11 uncomplicated cases (p ϭ 0.005 with Kruskal-Wallis test). EV71 cases with pulmonary edema had a significantly lower PHA stimulation index (p ϭ 0.04, measured to compare the percentages of a response over the median level of increase of all the EV71 cases by using likelihood ratio 2 test). abstract: We valuated specific cellular and humoral immune response of cases of enterovirus 71 (EV71) infection and correlated immune response with clinical outcome. After obtaining informed consent, we enrolled 30 EV71 cases including 7 cases with brainstem encephalitis plus pulmonary edema, 12 cases of CNS (CNS) involvement and 11 uncomplicated cases. We measured antibodies specific to EV71, lymphocyte proliferation response and EV71-stimulated cellular response of Th1/Th2 cytokines and chemokines. The 7 EV71 cases involving brainstem encephalitis plus pulmonary edema had a significantly lower phytohemagglutinin stimulation index than other cases (p = 0.04). After EV71 stimulation of peripheral mononuclear cells, there was a significant increase in cellular Th1 cytokine (γ-interferon) and proinflammatroy cytokines. However, cases with pulmonary edema had significantly lower cellular γ-interferon (p = 0.04), lower cellular IL-1β (p = 0.04), lower cellular IL-6 (p = 0.04), lower cellular tumor necrosis factor-α response (p = 0.04), and lower cellular macrophage inflammatory protein-1α (p = 0.04) response compared with other cases. Their titers of EV71 neutralizing antibodies demonstrated no difference among cases. These results suggest lower EV71-specific cellular response may be associated with immunopathogenesis of EV71-related pulmonary edema. url: https://www.ncbi.nlm.nih.gov/pubmed/16940249/ doi: 10.1203/01.pdr.0000238247.86041.19 id: cord-001017-4qfhltg4 author: Chatterjee, Dhriti title: Microglia Play a Major Role in Direct Viral-Induced Demyelination date: 2013-06-20 words: 6654.0 sentences: 312.0 pages: flesch: 42.0 cache: ./cache/cord-001017-4qfhltg4.txt txt: ./txt/cord-001017-4qfhltg4.txt summary: Previous studies demonstrated that microglia can be persistently infected by neurotropic mouse hepatitis virus (MHV) which causes meningoencephalitis, myelitis with subsequent axonal loss, and demyelination and serve as a virus-induced model of human neurological disease multiple sclerosis (MS). In our current studies, we have used RSA59 infection in vivo, in vitro, and ex vivo as a model to understand whether MHV can directly infect CNS resident microglia and the mechanism of microglial activation in the induction of chronic demyelination. To confirm the RSA59-induced CNS inflammation, brain and spinal cord sections from day 7 (peak of inflammation) and day 30 (peak of demyelination) postinfected mice were stained with H&E or LFB and examined. While Iba1 immunofluorescence was observed in both gray and white matter, double fluorescence/immunofluorescence demonstrated dual labelling of EGFP (viral antigen) positive Iba1 positive microglia/macrophages were present only in the white matter of RSA59 infected mice (Figure 1 ). abstract: Microglia are the resident macrophage-like populations in the central nervous system (CNS). Microglia remain quiescent, unable to perform effector and antigen presentation (APC) functions until activated by injury or infection, and have been suggested to represent the first line of defence for the CNS. Previous studies demonstrated that microglia can be persistently infected by neurotropic mouse hepatitis virus (MHV) which causes meningoencephalitis, myelitis with subsequent axonal loss, and demyelination and serve as a virus-induced model of human neurological disease multiple sclerosis (MS). Current studies revealed that MHV infection is associated with the pronounced activation of microglia during acute inflammation, as evidenced by characteristic changes in cellular morphology and increased expression of microglia-specific proteins, Iba1 (ionized calcium-binding adaptor molecule 1), which is a macrophage/microglia-specific novel calcium-binding protein and involved in membrane ruffling and phagocytosis. During chronic inflammation (day 30 postinfection), microglia were still present within areas of demyelination. Experiments performed in ex vivo spinal cord slice culture and in vitro neonatal microglial culture confirmed direct microglial infection. Our results suggest that MHV can directly infect and activate microglia during acute inflammation, which in turn during chronic inflammation stage causes phagocytosis of myelin sheath leading to chronic inflammatory demyelination. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705805/ doi: 10.1155/2013/510396 id: cord-337365-hugenn14 author: Chen, Zhuangzhuang title: The role of microglia in viral encephalitis: a review date: 2019-04-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Viral encephalitis is still very prominent around the world, and traditional antiviral therapies still have shortcomings. Some patients cannot get effective relief or suffer from serious sequelae. At present, people are studying the role of the innate immune system in viral encephalitis. Microglia, as resident cells of the central nervous system (CNS), can respond quickly to various CNS injuries including trauma, ischemia, and infection and maintain the homeostasis of CNS, but this response is not always good; sometimes, it will exacerbate damage. Studies have shown that microglia also act as a double-edged sword during viral encephalitis. On the one hand, microglia can sense ATP signals through the purinergic receptor P2Y12 and are recruited around infected neurons to exert phagocytic activity. Microglia can exert a direct antiviral effect by producing type 1 interferon (IFN-1) to induce IFN-stimulated gene (ISG) expression of themselves or indirect antiviral effects by IFN-1 acting on other cells to activate corresponding signaling pathways. In addition, microglia can also exert an antiviral effect by inducing autophagy or secreting cytokines. On the other hand, microglia mediate presynaptic membrane damage in the hippocampus through complement, resulting in long-term memory impairment and cognitive dysfunction in patients with encephalitis. Microglia mediate fetal congenital malformations caused by Zika virus (ZIKV) infection. The gene expression profile of microglia in HIV encephalitis changes, and they tend to be a pro-inflammatory type. Microglia inhibited neuronal autophagy and aggravated the damage of CNS in HIV encephalitis; E3 ubiquitin ligase Pellino (pelia) expressed by microglia promotes the replication of virus in neurons. The interaction between amyloid-β peptide (Aβ) produced by neurons and activated microglia during viral infection is uncertain. Although neurons can mediate antiviral effects by activating receptor-interacting protein kinases 3 (RIPK3) in a death-independent pathway, the RIPK3 pathway of microglia is unknown. Different brain regions have different susceptibility to viruses, and the gene expression of microglia in different brain regions is specific. The relationship between the two needs to be further confirmed. How to properly regulate the function of microglia and make it exert more anti-inflammatory effects is our next research direction. url: https://doi.org/10.1186/s12974-019-1443-2 doi: 10.1186/s12974-019-1443-2 id: cord-259347-3acsko74 author: Cheng, Qi title: Infectivity of human coronavirus in the brain date: 2020-05-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A new strain of human coronaviruses (hCoVs), Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has been identified to be responsible for the current outbreak of the coronavirus disease 2019 (COVID-19). Though major symptoms are primarily generated from the respiratory system, neurological symptoms are being reported in some of the confirmed cases, raising concerns of its potential for intracranial invasion and neurological manifestations, both in the acute phase and in the long-term. At present, it remains unclear the extent to which SARS-CoV-2 is present in the brain, and if so, its pathogenic role in the central nervous system (CNS). Evidence for neuroinvasion and neurovirulence of hCoVs has been recognised in animal and human studies. Given that SARS-CoV-2 belongs to the same family and shares characteristics in terms of receptor binding properties, it is worthwhile exploring its potential CNS manifestations. This review summarises previous findings from hCoVs in relation to the CNS, and compares these with the new strain, aiming to provide a better understanding of the effects of SARS-CoV-2 on the CNS. url: https://www.ncbi.nlm.nih.gov/pubmed/32474399/ doi: 10.1016/j.ebiom.2020.102799 id: cord-290566-tmsocyfc author: Chitnis, Tanuja title: The Role of CD4 T Cells in the Pathogenesis of Multiple Sclerosis date: 2007-05-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: T lymphocytes play a central role in the pathogenesis of multiple sclerosis (MS) (Zhang et al., 1992). Both CD4+ and CD8+ T cells have been demonstrated in MS lesions, with CD4+ T cells predominating in acute lesions and CD8+ T cells being observed more frequently in chronic lesions (Raine, 1994). Additionally, T cells are found in all four of the described histopathologic subtypes of MS (Lucchinetti et al., 2000). Activated myelin‐reactive CD4+ T cells are present in the blood and cerebrospinal fluid (CSF) of MS patients; in contrast, only nonactivated myelin‐reactive T cells are present in the blood of controls (Zhang et al., 1994). The success of several T‐cell‐targeted therapies in MS reinforces the importance of the role of the T cell in MS pathogenesis. Here, we outline basic concepts in CD4+ T‐cell immunology and summarize the current understanding of the role of CD4+ T cells in the pathogenesis of MS. url: https://www.ncbi.nlm.nih.gov/pubmed/17531837/ doi: 10.1016/s0074-7742(07)79003-7 id: cord-017954-vobslprh author: Croxford, J. Ludovic title: Animal Models for the Study of Neuroimmunological Disease date: 2016-03-26 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The development and use of numerous animal models of human autoimmune diseases have provided important advances in our understanding of pathogenic mechanisms of disease and provided robust and reliable models to test novel therapeutic strategies. However, few preclinical studies of therapeutic treatments have demonstrated efficacy in the clinic, possibly because of the biological differences between humans and other animals. Although animal models of human disease are imperfect, it is important to understand the differences between the human disease and its animal models and to design experimental studies using animal models appropriately for the questions being asked. This review provides an overview of the currently used animal models of three human neuroimmunological diseases, multiple sclerosis, Guillain-Barré syndrome, and myasthenia gravis, as well as the advantages and disadvantages of each model and how they correlate or differ from their human counterpart. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122656/ doi: 10.1007/978-4-431-55594-0_3 id: cord-294812-nnlzwaf1 author: Desforges, Marc title: Neuroinvasive and Neurotropic Human Respiratory Coronaviruses: Potential Neurovirulent Agents in Humans date: 2014-03-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: In humans, viral infections of the respiratory tract are a leading cause of morbidity and mortality worldwide. Several recognized respiratory viral agents have a neuroinvasive capacity since they can spread from the respiratory tract to the central nervous system (CNS). Once there, infection of CNS cells (neurotropism) could lead to human health problems, such as encephalitis and long-term neurological diseases. Among the various respiratory viruses, coronaviruses are important pathogens of humans and animals. Human Coronaviruses (HCoV) usually infect the upper respiratory tract, where they are mainly associated with common colds. However, in more vulnerable populations, such as newborns, infants, the elderly, and immune-compromised individuals, they can also affect the lower respiratory tract, leading to pneumonia, exacerbations of asthma, respiratory distress syndrome, or even severe acute respiratory syndrome (SARS). The respiratory involvement of HCoV has been clearly established since the 1960s. In addition, for almost three decades now, the scientific literature has also demonstrated that HCoV are neuroinvasive and neurotropic and could induce an overactivation of the immune system, in part by participating in the activation of autoreactive immune cells that could be associated with autoimmunity in susceptible individuals. Furthermore, it was shown that in the murine CNS, neurons are the main target of infection, which causes these essential cells to undergo degeneration and eventually die by some form of programmed cell death after virus infection. Moreover, it appears that the viral surface glycoprotein (S) represents an important factor in the neurodegenerative process. Given all these properties, it has been suggested that these recognized human respiratory pathogens could be associated with the triggering or the exacerbation of neurological diseases for which the etiology remains unknown or poorly understood. url: https://doi.org/10.1007/978-81-322-1777-0_6 doi: 10.1007/978-81-322-1777-0_6 id: cord-308201-lavcsqov author: Desforges, Marc title: Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System? date: 2019-12-20 words: 8470.0 sentences: 473.0 pages: flesch: 36.0 cache: ./cache/cord-308201-lavcsqov.txt txt: ./txt/cord-308201-lavcsqov.txt summary: Viruses infecting human CNS cells could then cause different types of encephalopathy, including encephalitis, and long-term neurological diseases. Even though no clear cause and effect link has ever been made with the onset of human neurological diseases, their neuropathogenicity is being increasingly recognized in humans, as several recent reports associated cases of encephalitis [244] , acute flaccid paralysis [271] and other neurological symptoms, including possible complications of HCoV infection such as Guillain-Barré syndrome or ADEM [249, [272] [273] [274] [275] [276] [277] [278] [279] . Like for several other respiratory viruses, accumulating evidence now indicate that HCoV are neuroinvasive in humans and we hypothesize that these recognized respiratory pathogens are potentially neurovirulent as well, as they could participate in short-and long-term neurological disorders either as a result of inadequate host immune responses and/or viral propagation in the CNS, which directly induces damage to resident cells. abstract: Respiratory viruses infect the human upper respiratory tract, mostly causing mild diseases. However, in vulnerable populations, such as newborns, infants, the elderly and immune-compromised individuals, these opportunistic pathogens can also affect the lower respiratory tract, causing a more severe disease (e.g., pneumonia). Respiratory viruses can also exacerbate asthma and lead to various types of respiratory distress syndromes. Furthermore, as they can adapt fast and cross the species barrier, some of these pathogens, like influenza A and SARS-CoV, have occasionally caused epidemics or pandemics, and were associated with more serious clinical diseases and even mortality. For a few decades now, data reported in the scientific literature has also demonstrated that several respiratory viruses have neuroinvasive capacities, since they can spread from the respiratory tract to the central nervous system (CNS). Viruses infecting human CNS cells could then cause different types of encephalopathy, including encephalitis, and long-term neurological diseases. Like other well-recognized neuroinvasive human viruses, respiratory viruses may damage the CNS as a result of misdirected host immune responses that could be associated with autoimmunity in susceptible individuals (virus-induced neuro-immunopathology) and/or viral replication, which directly causes damage to CNS cells (virus-induced neuropathology). The etiological agent of several neurological disorders remains unidentified. Opportunistic human respiratory pathogens could be associated with the triggering or the exacerbation of these disorders whose etiology remains poorly understood. Herein, we present a global portrait of some of the most prevalent or emerging human respiratory viruses that have been associated with possible pathogenic processes in CNS infection, with a special emphasis on human coronaviruses. url: https://doi.org/10.3390/v12010014 doi: 10.3390/v12010014 id: cord-353242-9vy8k6du author: Dhaiban, Sarah title: Targeting Chemokines and Chemokine Receptors in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis date: 2020-09-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Multiple sclerosis (MS) is an immune-mediated and neurodegenerative disorder that results in inflammation and demyelination of the central nervous system (CNS). MS symptoms include walking difficulties, visual weakening, as well as learning and memory impairment, thus affecting the quality of the patient’s life. Chemokines and chemokine receptors are expressed on the immune cells as well as the CNS resident cells. Several sets of chemokine receptors and their ligands tend to be pathogenic players in MS, including CCL2, CCL3, CCL4, CCL5, CCL7, CCL8, CCL11, CCL17, CCL19, CCL21, CCL22, CXCL1, CXCL8, CXCL9, CXCL10, CXCL11, and CXCL16. Furthermore, current modulatory drugs that are used in the treatment of MS and its animal model, the experimental autoimmune encephalomyelitis (EAE), affect the expression of several chemokine and chemokine receptors. In this review, we highlight the pathogenic roles of chemokines and their receptors as well as utilizing them as potential therapeutic targets through selective agents, such as specific antibodies and receptor blockers, or indirectly through MS or EAE immunomodulatory drugs. url: https://www.ncbi.nlm.nih.gov/pubmed/33061527/ doi: 10.2147/jir.s270872 id: cord-274315-08mk8a86 author: DiSano, Krista D. title: An optimized method for enumerating CNS derived memory B cells during viral-induced inflammation date: 2017-06-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract Background CNS inflammation resulting from infection, injury, or neurodegeneration leads to accumulation of diverse B cell subsets. Although antibody secreting cells (ASC) within the inflamed CNS have been extensively examined, memory B cell (Bmem) characterization has been limited as they do not secrete antibody without stimulation. Moreover, unlike human Bmem, reliable surface markers for murine Bmem remain elusive. New method Using a viral encephalomyelitis model we developed a modified limiting dilution in vitro stimulation assay to convert CNS-derived virus specific Bmem into ASC. Comparison with existing methods Stimulation methods established for lymphoid tissue cells using prolonged stimulation with viral lysate resulted in substantial ASC loss and minimal Bmem to ASC conversion of CNS-derived cells. By varying stimulation duration, TLR activators, and culture supplements, we achieved optimal conversion by culturing cells with TLR7/8 agonist R848 in the presence of feeder cells for 2days. Results Flow cytometry markers CD38 and CD73 characterizing murine Bmem from lymphoid tissue showed more diverse expression patterns on corresponding CNS-derived B cell subsets. Using the optimized TLR7/8 stimulation protocol, we compared virus-specific IgG Bmem versus pre-existing ASC within the brain and spinal cord. Increasing Bmem frequencies during chronic infection mirrored kinetics of ASC. However, despite initially similar Bmem and ASC accumulation, Bmem prevailed in the brain, but were lower than ASC in the spinal cord during persistence. Conclusion Simultaneous enumeration of antigen-specific Bmem and ASC using the Bmem assay optimized for CNS-derived cells enables characterization of temporal changes during microbial or auto-antigen induced neuroinflammation. url: https://doi.org/10.1016/j.jneumeth.2017.05.011 doi: 10.1016/j.jneumeth.2017.05.011 id: cord-253797-a9lmfaho author: Eddleston, M. title: Molecular profile of reactive astrocytes—Implications for their role in neurologic disease date: 1993-05-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract The central nervous system responds to diverse neurologic injuries with a vigorous activation of astrocytes. While this phenomenon is found in many different species, its function is obscure. Understanding the molecular profile characteristic of reactive astrocytes should help define their function. The purpose of this review is to provide a summary of molecules whose levels of expression differentiate activated from resting astrocytes and to use the molecular profile of reactive astrocytes as the basis for speculations on the functions of these cells. At present, reactive astrocytosis is defined primarily as an increase in the number and size of cells expressing glial fibrillary acidic protein. In vivo, this increase in glial fibrillary acidic protein-positive cells reflects predominantly phenotypic changes of resident astroglia rather than migration or proliferation of such cells. Upon activation, astrocytes upmodulate the expression of a large number of molecules. From this molecular profile it becomes apparent that reactive astrocytes may benefit the injured nervous system by participating in diverse biological processes. For example, upregulation of proteases and protease inhibitors could help remodel the extracellular matrix, regulate the concentration of different proteins in the neuropil and clear up debris from degenerating cells. Cytokines are key mediators of immunity and inflammation and could play a critical role in the regulation of the blood-central nervous system interface. Neurotrophic factors, transporter molecules and enzymes involved in the metabolism of excitotoxic amino acids or in the antioxidant pathway may help protect neurons and other brain cells by controlling neurotoxin levels and contributing to homeostasis within the central nervous system. Therefore, an impairment of astroglial performance has the potential to exacerbate neuronal dysfunction. Based on the synopsis of studies presented, a number of issues become apparent that deserve a more extensive analysis. Among them are the relative contribution of microglia and astrocytes to early wound repair, the characterization of astroglial subpopulations, the specificity of the astroglial response in different diseases as well as the analysis of reactive astrocytes with techniques that can resolve fast physiologic processes. Differences between reactive astrocytes in vivo and primary astrocytes in culture are discussed and underline the need for the development and exploitation of models that will allow the analysis of reactive astrocytes in the intact organism. url: https://www.sciencedirect.com/science/article/pii/030645229390380X doi: 10.1016/0306-4522(93)90380-x id: cord-348746-yaf61cmx author: Foley, Janet E. title: A Review of Coronavirus Infection in the Central Nervous System of Cats and Mice date: 2008-06-28 words: 5478.0 sentences: 323.0 pages: flesch: 37.0 cache: ./cache/cord-348746-yaf61cmx.txt txt: ./txt/cord-348746-yaf61cmx.txt summary: F eline infectious peritonitis (FIP) is a fatal, immune-mediated disease produced as a result of infection of macrophages by mutant feline coronavirus strains (FIPVs). In acute MHV-A59 infection in CD8ϩ T-cell deficient mice, periventricular encephalitis occurs with lymphocytic infiltration into the choroid plexus, ependyma, and subependymal brain tissue. Depending on mouse strain and immunological status, MHV-JHM produces meningeal inflammation associated with T-cells and macrophages and demyelination but relatively little disease in axons. If mice are pretreated with passive infusions of antibodies or T-cells or if they receive neuroattenuated MHV strains, they develop chronic, but not fatal, disease after MHV-JHM infection. 62, 63 Immunocompetent C57BL/6 mice clear MHV-JHM virus from the brain but develop severe immune-mediated demyelination and paralysis. Two related strains of feline infectious peritonitis virus isolated from immunocompromised cats infected with a feline enteric coronavirus abstract: Feline infectious peritonitis (FIP) is a common cause of death in cats. Management of this disease has been hampered by difficulties identifying the infection and determining the immunological status of affected cats and by high variability in the clinical, pathological, and immunological characteristics of affected cats. Neurological FIP, which is much more homogeneous than systemic effusive or noneffusive FIP, appears to be a good model for establishing the basic features of FIP immunopathogenesis. Very little information is available about the immunopathogenesis of neurologic FIP, and it is reasonable to use research from the well‐characterized mouse hepatitis virus (MHV) immune‐mediated encephalitis system, as a template for FIP investigation, and to contrast findings from the MHV model with those of FIP. It is expected that the immunopathogenic mechanisms will have important similarities. Such comparative research may lead to better understanding of FIP immunopathogenesis and rational prospects for management of this frustrating disease. url: https://www.ncbi.nlm.nih.gov/pubmed/11596730/ doi: 10.1111/j.1939-1676.2001.tb01572.x id: cord-026031-hnf5vayd author: Ford, Richard B. title: Emergency Care date: 2009-05-21 words: 112343.0 sentences: 6645.0 pages: flesch: 44.0 cache: ./cache/cord-026031-hnf5vayd.txt txt: ./txt/cord-026031-hnf5vayd.txt summary: Fresh whole blood Coagulopathy with active hemorrhage (disseminated intravascular coagulation, thrombocytopenia; massive acute hemorrhage; no stored blood available) Stored whole blood Massive acute or ongoing hemorrhage; hypovolemic shock caused by hemorrhage that is unresponsive to conventional crystalloid and colloid fluid therapy; unavailability of equipment required to prepare blood components Packed red blood cells Nonregenerative anemia, immune-mediated hemolytic anemia, correction of anemia before surgery, acute or chronic blood loss Fresh frozen plasma Factor depletion associated with active hemorrhage (congenital: von Willebrand''s factor, hemophilia A, hemophilia B; acquired: vitamin K antagonist, rodenticide intoxication, DIC); acute or chronic hypoproteinemia (burns, wound exudates, body cavity effusion; hepatic, renal, or gastrointestinal loss); colostrum replacement in neonates Frozen plasma Acute plasma or protein loss; chronic hypoproteinemia; (contains stable colostrum replacement in neonates; hemophilia B and clotting factors) selected clotting factor deficiencies Platelet-rich plasma* Thrombocytopenia with active hemorrhage (immune-mediated thrombocytopenia, DIC); platelet function abnormality (congenital: thrombasthenia in Bassett hounds; acquired: NSAIDs, other drugs) Cryoprecipitate abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271342/ doi: 10.1016/b0-72-160138-3/50002-3 id: cord-270458-7imgvale author: Franchini, Massimo title: The impact of the SARS‐CoV‐2 outbreak on the safety and availability of blood transfusions in Italy date: 2020-04-13 words: 1525.0 sentences: 78.0 pages: flesch: 50.0 cache: ./cache/cord-270458-7imgvale.txt txt: ./txt/cord-270458-7imgvale.txt summary: The CNS has already released since 22 January 2020 a recommendation outlining preventative measures for the transmission of SARS-CoV-2 by transfusion of labile blood components related to travels from the People''s Republic of China. On 2 March 2020, following the recommendations of the European Centre for Disease Prevention and Control (ECDC) [9] and reflecting the decrees of the Italian government, the CNS updated the prevention measures, reducing the period of temporary deferral of donors from the previous 28 to 14 days. Following the declaration of the government of the widespread dissemination of the SARS-CoV-2 infection in Italy, the last update of the CNS on 10 March 2020 extended these measures to the whole national territory of Italy. In Fig. 1 , the trend of positive cases for SARS-CoV-2 infection in Italy, updated on 20 March 2020, is reported with a concise chronology of the main documents released and the trend of blood donations in the same period. abstract: Coronaviruses are enveloped single-stranded RNA viruses belonging to the family of Coronaviridae. While initial research focused on their ability to cause enzootic infections, infections which have emerged in the past two decades demonstrate their ability to cross the species barrier and infect humans [1,2]. The ensuing epidemics have included Severe Acute Respiratory Syndrome (SARS) in 2002 and the more recent Middle East Respiratory Syndrome (MERS) in 2012, and have resulted in severe disease burden, mortality and economic disruption [3]. A novel flu-like coronavirus, emerging towards the end of 2019 and subsequently named SARS-CoV-2, has been associated with an epidemic initially focused in Wuhan, China. url: https://doi.org/10.1111/vox.12928 doi: 10.1111/vox.12928 id: cord-017499-51yy7y9n author: Freye, Enno title: Mechanism of Action of Opioids and Clinical Effects date: 2008 words: 24955.0 sentences: 1278.0 pages: flesch: 45.0 cache: ./cache/cord-017499-51yy7y9n.txt txt: ./txt/cord-017499-51yy7y9n.txt summary: Thus, -selective opioids like morphine, fentanyl and sufentanil, due to the high density of binding sites, mediate their main action within the brain stem and the midbrain. This sterospecificity of opiate action supports the concept of selective receptor binding to a site, which is able to distinguish in "handedness or goodness of fit" of an opioid molecule maximal response induced by administration of the active agent. On the other hand mixed agonist/antagonists, such as pentazocine, nalorphine, levallorphan, nalbuphine and butorphanol, demonstrate characteristics, which enable them to displace a pure agonist at the receptor site (antagonistic effect), but at the same time when administered by themselves, they induce opioid related effects such as analgesia and respiratory depression (agonistic effects; Table II-7) . However, a less potent opioid like codeine or tramadol, even when given in dosages higher than their therapeutic margin, will not induce a clinically relevant respiratory depressive effect ( Figure II-34) . abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122075/ doi: 10.1007/978-1-4020-5947-6_2 id: cord-002119-kl431ev6 author: Garcia, Elisa title: Cytokine and Growth Factor Activation In Vivo and In Vitro after Spinal Cord Injury date: 2016-06-23 words: 13445.0 sentences: 687.0 pages: flesch: 41.0 cache: ./cache/cord-002119-kl431ev6.txt txt: ./txt/cord-002119-kl431ev6.txt summary: Specific inflammatory cytokines such as TNF , IL-1, and IL-6 are synthetized by various cells in the CNS and are known as mediators of the peripheral immune response 8 [118, 192] IL-4 (i) High levels 24 h AI, concentrations remain during 7 days and decrease 3 days AI (i) Neuroinflammatory regulation in various pathological conditions (ii) Confers regenerative properties to macrophages (iii) Controls free radical production in peripheral macrophages and microglia [166, [193] [194] [195] [196] [197] [198] [199] IL-13 (i) Detected 1 day AI (i) Macrophage activation onto M2 phenotype [166, 199] IP-10/CXCL10 (i) Expressed locally 30 [200, [205] [206] [207] Mediators of Inflammation 9 [200, [205] [206] [207] MCP1/CCL2 (i) Detected from 1 h AI with PL at 24 h and remains low up to 24 days AI (i) Macrophage and PMN infiltration mediator [106, 184, 200, 205, 206] min: minutes; AI: after injury; PL: peak levels. abstract: Spinal cord injury results in a life-disrupting series of deleterious interconnected mechanisms encompassed by the primary and secondary injury. These events are mediated by the upregulation of genes with roles in inflammation, transcription, and signaling proteins. In particular, cytokines and growth factors are signaling proteins that have important roles in the pathophysiology of SCI. The balance between the proinflammatory and anti-inflammatory effects of these molecules plays a critical role in the progression and outcome of the lesion. The excessive inflammatory Th1 and Th17 phenotypes observed after SCI tilt the scale towards a proinflammatory environment, which exacerbates the deleterious mechanisms present after the injury. These mechanisms include the disruption of the spinal cord blood barrier, edema and ion imbalance, in particular intracellular calcium and sodium concentrations, glutamate excitotoxicity, free radicals, and the inflammatory response contributing to the neurodegenerative process which is characterized by demyelination and apoptosis of neuronal tissue. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4935915/ doi: 10.1155/2016/9476020 id: cord-316227-dgyxbgvg author: Geginat, Jens title: The Enigmatic Role of Viruses in Multiple Sclerosis: Molecular Mimicry or Disturbed Immune Surveillance? date: 2017-05-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Multiple sclerosis (MS) is a T cell driven autoimmune disease of the central nervous system (CNS). Despite its association with Epstein-Barr Virus (EBV), how viral infections promote MS remains unclear. However, there is increasing evidence that the CNS is continuously surveyed by virus-specific T cells, which protect against reactivating neurotropic viruses. Here, we discuss how viral infections could lead to the breakdown of self-tolerance in genetically predisposed individuals, and how the reactivations of viruses in the CNS could induce the recruitment of both autoaggressive and virus-specific T cell subsets, causing relapses and progressive disability. A disturbed immune surveillance in MS would explain several experimental findings, and has important implications for prognosis and therapy. url: https://www.ncbi.nlm.nih.gov/pubmed/28549714/ doi: 10.1016/j.it.2017.04.006 id: cord-011533-im78xwl8 author: Gloude, Nicholas J. title: Thinking Beyond HLH: Clinical Features of Patients with Concurrent Presentation of Hemophagocytic Lymphohistiocytosis and Thrombotic Microangiopathy date: 2020-05-23 words: 4879.0 sentences: 262.0 pages: flesch: 37.0 cache: ./cache/cord-011533-im78xwl8.txt txt: ./txt/cord-011533-im78xwl8.txt summary: MODS was diagnosed when a patient had symptoms of HLH/TMA and dysfunction of two or more organ systems: renal failure requiring renal replacement therapy (RRT) or cystatin C glomerular filtration rate (GFR) < 50 mL/min, invasive or non-invasive positive pressure ventilator support for > 24 h, diagnosis of pulmonary hypertension (as determined by echocardiogram and cardiology consultation), serositis (pleural or pericardial effusions), severe hypertension requiring either ≥ 2 medications or continuous infusion of an antihypertensive for > 12 h to maintain blood pressure < 99% for age, CNS symptoms (seizures, bleeding, posterior reversible encephalopathy syndrome (PRES), or altered mental status), or gastrointestinal symptoms (ileus and/or bleeding) [20] [21] [22] [23] [24] . We observed a high incidence of clinically significant complement-mediated thrombotic microangiopathy (TMA) associated with multi-organ injury in children and young adults with a diagnosis of HLH. abstract: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive immune system activation driven mainly by high levels of interferon gamma. The clinical presentation of HLH can have considerable overlap with other inflammatory conditions. We present a cohort of patients with therapy refractory HLH referred to our center who were found to have a simultaneous presentation of complement-mediated thrombotic microangiopathy (TMA). Twenty-three patients had therapy refractory HLH (13 primary, 4 EVB-HLH, 6 HLH without known trigger). Sixteen (69.6%) met high-risk TMA criteria. Renal failure requiring renal replacement therapy, severe hypertension, serositis, and gastrointestinal bleeding were documented only in patients with HLH who had concomitant complement-mediated TMA. Patients with HLH and without TMA required ventilator support mainly due to CNS symptoms, while those with HLH and TMA had respiratory failure predominantly associated with pulmonary hypertension, a known presentation of pulmonary TMA. Ten patients received eculizumab for complement-mediated TMA management while being treated for HLH. All patients who received the complement blocker eculizumab in addition to the interferon gamma blocker emapalumab had complete resolution of their TMA and survived. Our observations suggest co-activation of both interferon and complement pathways as a potential culprit in the evolution of thrombotic microangiopathy in patients with inflammatory disorders like refractory HLH and may offer novel therapeutic approaches for these critically ill patients. TMA should be considered in children with HLH and multi-organ failure, as an early institution of a brief course of complement blocking therapy in addition to HLH-targeted therapy may improve clinical outcomes in these patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10875-020-00789-4) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245179/ doi: 10.1007/s10875-020-00789-4 id: cord-009577-29u7pdpk author: Gonzalez‐Scarano, F. title: Molecular pathogenesis of neurotropic viral infections date: 2004-10-08 words: 6374.0 sentences: 294.0 pages: flesch: 41.0 cache: ./cache/cord-009577-29u7pdpk.txt txt: ./txt/cord-009577-29u7pdpk.txt summary: To cause systemic illness, a virus must first enter the host animal, undergo primary replication at a site near its portal of entry, and then ultimately spread to distant target tissues, such as the central nervous system (CNS). An infecting animal virus faces two main blocks to penetration of the CNS or any other specific target organ: (1) a variety of barriers prevent the free access of viruses to target cells, and (2) even when these barriers are ineffective, only certain cell types will support the internalization and replication of a particular virus. Monoclonal antibody variants have been used to map the antigenic sites of the influenza hemagglutinin 122, 76, 771 and have been used successfully to define important regions of the cellular binding proteins of rabies virus, reovirus, coronaviruses, and the California serogroup-all CNS pathogens. Viruses bind to the plasma membrane of susceptible target cells through specific receptors which may be proteins (HIV), lipids (vesicular stomatitis virus), or contain sialic acid (reovirus, influenza) [21, 641. abstract: Classical virologists defined a number of viruses that affect the nervous system and identified tissue tropism, extraneural replication, and viremia as important parameters that determine whether viral infections will affect the central nervous system. Molecular techniques are expanding this knowledge by permitting us to relate specific genes and gene products to two defined phenotypes: neuroinvasion and neurovirulence. Two converging situations make this knowledge particularly useful: (1) the development of antiviral drugs and subunit vaccines, which mandate that pathogenesis be related to specific regions of the viral genome; and (2) the expanding problem of central nervous system infections in immunodeficient states. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159691/ doi: 10.1002/ana.410220502 id: cord-278684-txlvla0j author: Gonzalez–Dunia, Daniel title: Borna Disease Virus and the Brain date: 1998-01-30 words: 13952.0 sentences: 784.0 pages: flesch: 43.0 cache: ./cache/cord-278684-txlvla0j.txt txt: ./txt/cord-278684-txlvla0j.txt summary: The BDV paradigm is amenable to study virus–cell interactions in the CNS that can lead to neurodevelopmental abnormalities, immune-mediated damage, as well as alterations in cell differentiated functions that affect brain homeostasis. Evidence provided by epidemiological and clinical data, together with virological studies, have led to the hypothesis that chronic viral infections of the CNS contribute to human mental disorders of unknown etiology. Therefore, neuronal damage seen in BD appears to be mediated by the cytotoxic activity of CD8 ϩ T-cells present in the brain parenchyma of BDV-infected rats. Studies on PTI-NB rats may provide valuable information regarding the contribution of CNS resident cells to disturbances in cytokine gene expression caused by BDV. Borna disease virus replicates in astrocytes, Schwann cells and ependymal cells in persistently infected rats: Location of viral genomic and messenger RNAs by in situ hybridization Expression of tissue factor is increased in astrocytes within the central nervous system during persistent infection with Borna disease virus abstract: Viruses with the ability to establish persistent infection in the central nervous system (CNS) can induce progressive neurologic disorders associated with diverse pathological manifestations. Clinical, epidemiological, and virological evidence supports the hypothesis that viruses contribute to human mental diseases whose etiology remains elusive. Therefore, the investigation of the mechanisms whereby viruses persist in the CNS and disturb normal brain function represents an area of research relevant to clinical and basic neurosciences. Borna disease virus (BDV) causes CNS disease in several vertebrate species characterized by behavioral abnormalities. Based on its unique features, BDV represents the prototype of a new virus family. BDV provides an important model for the investigation of the mechanisms and consequences of viral persistence in the CNS. The BDV paradigm is amenable to study virus–cell interactions in the CNS that can lead to neurodevelopmental abnormalities, immune-mediated damage, as well as alterations in cell differentiated functions that affect brain homeostasis. Moreover, seroepidemiological data and recent molecular studies indicate that BDV is associated with certain neuropsychiatric diseases. The potential role of BDV and of other yet to be uncovered BDV-related viruses in human mental health provides additional impetus for the investigation of this novel neurotropic infectious agent. url: https://api.elsevier.com/content/article/pii/S0361923097002761 doi: 10.1016/s0361-9230(97)00276-1 id: cord-271176-wdc4p4bc author: González-Scarano, Francisco title: Infectious etiology in multiple sclerosis: the debate continues date: 1999-12-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: ‘Demonstrating Infectious Cause: Viral and Bacterial Infections in MS and Related Disorders’ was held in Brighton, UK, 23–25 August 1999. url: https://api.elsevier.com/content/article/pii/S0966842X99016340 doi: 10.1016/s0966-842x(99)01634-0 id: cord-010187-ymhcfyxx author: Gromeier, Matthias title: Mouse neuropathogenic poliovirus strains cause damage in the central nervous system distinct from poliomyelitis date: 2005-03-25 words: 5144.0 sentences: 296.0 pages: flesch: 42.0 cache: ./cache/cord-010187-ymhcfyxx.txt txt: ./txt/cord-010187-ymhcfyxx.txt summary: We report a comparison of the clinical course and the histopathological features of neurological disease resulting from intracerebral virus inoculation in normal micewith those of murine poliomyelitis in hPVR-tg mice. Histopathological analysis showed a diffuse encephalomyelitis induced by specific poliovirus serotype 2 isolates in normal mice, that affected neuronal cell populations without discrimination, whereas in hPVR-tg animals, damage was restricted to spinal motor neurons. 6 The hPVR is a highly glycosylated protein with an apparent molecular weight of 80kDa2 The animal model for poliomyelitis in hPVR-tg mice showed PV-induced damage of comparable anatomical distribution as in primates, 1°''11 an observation confirming views of the hPVR as the critical determinant conferring PV susceptibility. None of the normal mice injected with PVI(M) showed clinical signs of neurological damage, whereas inoculation of type 2 PV strains produced signs of CNS infection ( Table 2) . abstract: Poliomyelitis as a consequence of poliovirus infection is observed only in primates. Despitea host range restricted to primates, experimental infection of rodents with certain genetically well defined poliovirus strains produces neurological disease. The outcome of infection of mice with mouse-adapted poliovirus strains has been described previously mainly in terms of paralysis and death, and it was generally assumed that these strains produce the same disease syndromes in normal mice and in mice transgenic for the human poliovirus receptor (hPVR-tg mice). We report a comparison of the clinical course and the histopathological features of neurological disease resulting from intracerebral virus inoculation in normal micewith those of murine poliomyelitis in hPVR-tg mice. The consistent pattern of clinical deficits in poliomyelitic transgenic mice contrasted with highly variable neurologic disease that developed in mice infected with different mouse-adapted polioviruses. Histopathological analysis showed a diffuse encephalomyelitis induced by specific poliovirus serotype 2 isolates in normal mice, that affected neuronal cell populations without discrimination, whereas in hPVR-tg animals, damage was restricted to spinal motor neurons. Mouse neurovirulent strains of poliovirus type 2 differed from mouse neurovirulent poliovirus type 1 derivatives in their ability to induce CNS lesions. Our findings indicate that the characteristic clinical appearance and highly specific histopathological features of poliomyelitis are mediated by the hPVR. Our data lead us to conclude that the tissue tropism of mouse-adapted poliovirus strains in normal mice is fundamentally different from that of poliovirus in hPVR-tg mice and primates, and that this is indicative of an as yet unknown mechanism of adsorption and uptake of the virus into cells of the murine CNS. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172458/ doi: 10.1016/s0882-4010(05)80002-6 id: cord-340008-2efzyki4 author: Haddadi, Kaveh title: Coronavirus Disease 2019: Latest Data on Neuroinvasive Potential date: 2020-09-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Coronavirus disease 2019 (COVID-19) is a pandemic infection. Similar to other respiratory viruses, severe acute respiratory syndrome coronavirus (SARS-COV-2) may enter the brain via the hematogenous or neuronal route; however, only a few reports are available on the neurological complications of COVID-19. Encephalopathy is a significant neurological complication of COVID-19. We herein present an update on the virology, neurological pathogenesis, and neuroinvasive potential of coronaviruses and briefly discuss the latest findings on SARS-CoV-2 neuroinfection. The reports thus far indicate that the access of SARS-CoV into host cells is bolstered chiefly by a cellular receptor, angiotensin-converting enzyme 2, and that SARS-CoV-2 may induce some neurological manifestations via direct or indirect mechanisms. Further research is required to shed sufficient light on the impact on the central nervous system and altered mental status in patients with COVID-19. Indeed, a better understanding of the pathways of SARS-CoV-2 neuroinvasion would further clarify the neurological pathogenesis and manifestations of coronaviruses and enhance the management and treatment of this group of patients. In the current epidemic era of COVID-19, health care staff should strongly become aware of SARS-CoV-2 infection as an essential diagnosis to get away misdiagnosis and prevention of transmission. url: https://doi.org/10.30476/ijms.2020.85980.1561 doi: 10.30476/ijms.2020.85980.1561 id: cord-262281-56tbrl8a author: Hawkes, C. H. title: Parkinson's disease: a dual‐hit hypothesis date: 2007-10-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Accumulating evidence suggests that sporadic Parkinson's disease has a long prodromal period during which several non‐motor features develop, in particular, impairment of olfaction, vagal dysfunction and sleep disorder. Early sites of Lewy pathology are the olfactory bulb and enteric plexus of the stomach. We propose that a neurotropic pathogen, probably viral, enters the brain via two routes: (i) nasal, with anterograde progression into the temporal lobe; and (ii) gastric, secondary to swallowing of nasal secretions in saliva. These secretions might contain a neurotropic pathogen that, after penetration of the epithelial lining, could enter axons of the Meissner's plexus and, via transsynaptic transmission, reach the preganglionic parasympathetic motor neurones of the vagus nerve. This would allow retrograde transport into the medulla and, from here, into the pons and midbrain until the substantia nigra is reached and typical aspects of disease commence. Evidence for this theory from the perspective of olfactory and autonomic dysfunction is reviewed, and the possible routes of pathogenic invasion are considered. It is concluded that the most parsimonious explanation for the initial events of sporadic Parkinson's disease is pathogenic access to the brain through the stomach and nose – hence the term ‘dual‐hit’. url: https://www.ncbi.nlm.nih.gov/pubmed/17961138/ doi: 10.1111/j.1365-2990.2007.00874.x id: cord-000725-rafwlw0t author: Hindinger, Claudia title: IFN-γ Signaling to Astrocytes Protects from Autoimmune Mediated Neurological Disability date: 2012-07-27 words: 5114.0 sentences: 243.0 pages: flesch: 37.0 cache: ./cache/cord-000725-rafwlw0t.txt txt: ./txt/cord-000725-rafwlw0t.txt summary: Experimental autoimmune encephalomyelitis (EAE) was induced in transgenic mice expressing signaling defective dominant-negative interferon gamma (IFN-γ) receptors on astrocytes to determine the influence of inflammation on astrocyte activity. Inhibition of IFN-γ signaling to astrocytes did not influence disease incidence, onset, initial progression of symptoms, blood brain barrier (BBB) integrity or the composition of the acute CNS inflammatory response. GFAPcR1D and wt mice were compared at the peak of acute disease to determine if IFN-c signaling altered astrocyte activation or CNS inflammation. Despite elevated demyelination and axonal loss in the absence of IFN-c signaling to astrocytes, spinal cords showed no evidence of differential astrocyte activation by either immunohistochemistry (Fig. 4 ), or differences in GFAP mRNA expression during the peak of acute disease (Fig. 5 ). Although demyelination was increased in the CNS of GFAPcR1D mice, the extent of astrocyte activation associated with spinal cord white matter lesions was similar in both groups ( Fig. 6 ; ,60 GFAP + cells/mm 2 ). abstract: Demyelination and axonal degeneration are determinants of progressive neurological disability in patients with multiple sclerosis (MS). Cells resident within the central nervous system (CNS) are active participants in development, progression and subsequent control of autoimmune disease; however, their individual contributions are not well understood. Astrocytes, the most abundant CNS cell type, are highly sensitive to environmental cues and are implicated in both detrimental and protective outcomes during autoimmune demyelination. Experimental autoimmune encephalomyelitis (EAE) was induced in transgenic mice expressing signaling defective dominant-negative interferon gamma (IFN-γ) receptors on astrocytes to determine the influence of inflammation on astrocyte activity. Inhibition of IFN-γ signaling to astrocytes did not influence disease incidence, onset, initial progression of symptoms, blood brain barrier (BBB) integrity or the composition of the acute CNS inflammatory response. Nevertheless, increased demyelination at peak acute disease in the absence of IFN-γ signaling to astrocytes correlated with sustained clinical symptoms. Following peak disease, diminished clinical remission, increased mortality and sustained astrocyte activation within the gray matter demonstrate a critical role of IFN-γ signaling to astrocytes in neuroprotection. Diminished disease remission was associated with escalating demyelination, axonal degeneration and sustained inflammation. The CNS infiltrating leukocyte composition was not altered; however, decreased IL-10 and IL-27 correlated with sustained disease. These data indicate that astrocytes play a critical role in limiting CNS autoimmune disease dependent upon a neuroprotective signaling pathway mediated by engagement of IFN-γ receptors. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407093/ doi: 10.1371/journal.pone.0042088 id: cord-001332-dp6vzgef author: Hosking, Martin P. title: ELR(+) chemokine signaling in host defense and disease in a viral model of central nervous system disease date: 2014-06-17 words: 2736.0 sentences: 152.0 pages: flesch: 31.0 cache: ./cache/cord-001332-dp6vzgef.txt txt: ./txt/cord-001332-dp6vzgef.txt summary: Intracranial infection of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the central nervous system (CNS) of susceptible strains of mice results in an acute encephalomyelitis, accompanied by viral replication in glial cells and robust infiltration of virus-specific T cells that contribute to host defense through cytokine secretion and cytolytic activity. Moreover, PMNs have been shown to enhance central nervous system (CNS) inflammation by disrupting blood brain barrier (BBB) integrity in animal models of spinal cord injury (SCI; Tonai et al., 2001; Gorio et al., 2007) , autoimmune demyelination (Carlson et al., 2008) , and JHMV-induced encephalomyelitis (Zhou et al., 2003) , while blocking or silencing of CXCR2 signaling mutes inflammation and tissue damage in mouse models in which PMN infiltration is critical to disease initiation (Kielian et al., 2001; Belperio et al., 2005; Londhe et al., 2005a,b; Strieter et al., 2005; Gorio et al., 2007; Wareing et al., 2007; Carlson et al., 2008) . abstract: Intracranial infection of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the central nervous system (CNS) of susceptible strains of mice results in an acute encephalomyelitis, accompanied by viral replication in glial cells and robust infiltration of virus-specific T cells that contribute to host defense through cytokine secretion and cytolytic activity. Mice surviving the acute stage of disease develop an immune-mediated demyelinating disease, characterized by viral persistence in white matter tracts and a chronic neuroinflammatory response dominated by T cells and macrophages. Chemokines and their corresponding chemokine receptors are dynamically expressed throughout viral infection of the CNS, influencing neuroinflammation by regulating immune cell infltration and glial biology. This review is focused upon the pleiotropic chemokine receptor CXCR2 and its effects upon neutrophils and oligodendrocytes during JHMV infection and a number of other models of CNS inflammation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4060560/ doi: 10.3389/fncel.2014.00165 id: cord-276587-ynionj5r author: Hwang, Mihyun title: Alpha/Beta Interferon (IFN-α/β) Signaling in Astrocytes Mediates Protection against Viral Encephalomyelitis and Regulates IFN-γ-Dependent Responses date: 2018-04-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The contribution of distinct central nervous system (CNS) resident cells to protective alpha/beta interferon (IFN-α/β) function following viral infections is poorly understood. Based on numerous immune regulatory functions of astrocytes, we evaluated the contribution of astrocyte IFN-α/β signaling toward protection against the nonlethal glia- and neuronotropic mouse hepatitis virus (MHV) strain A59. Analysis of gene expression associated with IFN-α/β function, e.g., pattern recognition receptors (PRRs) and interferon-stimulated genes (ISGs), revealed lower basal mRNA levels in brain-derived astrocytes than in microglia. Although astrocytes poorly induced Ifnβ mRNA following infection, they upregulated various mRNAs in the IFN-α/β pathway to a higher extent than microglia, supporting effective IFN-α/β responsiveness. Ablation of the IFN-α/β receptor (IFNAR) in astrocytes using mGFAPcre IFNAR(fl/fl) mice resulted in severe encephalomyelitis and mortality, coincident with uncontrolled virus replication. Further, virus spread was not restricted to astrocytes but also affected microglia and neurons, despite increased and sustained Ifnα/β and ISG mRNA levels within the CNS. IFN-γ, a crucial mediator for MHV control, was not impaired in infected mGFAPcre IFNAR(fl/fl) mice despite reduced T cell CNS infiltration. Unexpectedly however, poor induction of IFN-γ-dependent major histocompatibility complex (MHC) class II expression on microglia supported that defective IFN-γ signaling contributes to uncontrolled virus replication. A link between sustained elevated IFN-α/β and impaired responsiveness to IFN-γ supports the novel concept that temporally limited early IFN-α/β responses are critical for effective antiviral IFN-γ function. Overall, our results imply that IFN-α/β signaling in astrocytes is not only critical in limiting early CNS viral spread but also promotes protective antiviral IFN-γ function. IMPORTANCE An antiviral state established by IFN-α/β contains initial viral spread as adaptive immunity develops. While it is apparent that the CNS lacks professional IFN-α/β producers and that resident cells have distinct abilities to elicit innate IFN-α/β responses, protective interactions between inducer and responder cells require further investigation. Infection with a glia- and neuronotropic coronavirus demonstrates that astrocytes mount a delayed but more robust response to infection than microglia, despite their lower basal mRNA levels of IFN-α/β-inducing components. Lethal, uncontrolled viral dissemination following ablation of astrocyte IFN-α/β signaling revealed the importance of IFN-α/β responses in a single cell type for protection. Sustained global IFN-α/β expression associated with uncontrolled virus did not suffice to protect neurons and further impaired responsiveness to protective IFN-γ. The results support astrocytes as critical contributors to innate immunity and the concept that limited IFN-α/β responses are critical for effective subsequent antiviral IFN-γ function. url: https://doi.org/10.1128/jvi.01901-17 doi: 10.1128/jvi.01901-17 id: cord-345254-glm2dxhh author: Hwang, Mihyun title: Distinct CD4 T-cell effects on primary versus recall CD8 T-cell responses during viral encephalomyelitis date: 2015-02-13 words: 7372.0 sentences: 372.0 pages: flesch: 54.0 cache: ./cache/cord-345254-glm2dxhh.txt txt: ./txt/cord-345254-glm2dxhh.txt summary: By contrast, unhelped memory CD8 T cells mounted poor recall responses when transferred into CD4 T-cell-sufficient mice and could not be sustained in the CNS, despite efficient virus control. Donor mice were treated with anti-mouse CD4 or control mAb at day À2 and 0 relative to intraperitoneal immunization for comparative analysis of ''unhelped'' versus ''helped'' CD8 T cells. As T cells are the primary mediators of JHMV control in the CNS during the first 14 days p.i. 29, 30 the inability of CD4-depleted mice to reduce viral load suggested impaired CD8 T-cell recruitment or function. 15 We therefore examined potential defects in effector functions of brain-derived unhelped virus-specific CD8 T cells by measurement of ex vivo cytolytic activity and IFN-c expression. To generate unhelped or helped donor memory CD8 T cells, Thy-1.1 mice were either treated with anti-CD4 or control mAb before JHMV immunization. abstract: CD4 T-cell help is not a universal requirement for effective primary CD8 T cells but is essential to generate memory CD8 T cells capable of recall responses. This study examined how CD4 T cells affect primary and secondary anti-viral CD8 T-cell responses within the central nervous system (CNS) during encephalomyelitis induced by sublethal gliatropic coronavirus. CD4 T-cell depletion before infection did not impair peripheral expansion, interferon-γ production, CNS recruitment or initial CNS effector capacity of virus-specific CD8 T cells ex vivo. Nevertheless, impaired virus control in the absence of CD4 T cells was associated with gradually diminished CNS CD8 T-cell interferon-γ production. Furthermore, within the CD8 T-cell population short-lived effector cells were increased and memory precursor effector cells were significantly decreased, consistent with higher T-cell turnover. Transfer of memory CD8 T cells to reduce viral load in CD4-depleted mice reverted the recipient CNS CD8 T-cell phenotype to that in wild-type control mice. However, memory CD8 T cells primed without CD4 T cells and transferred into infected CD4-sufficient recipients expanded less efficiently and were not sustained in the CNS, contrasting with their helped counterparts. These data suggest that CD4 T cells are dispensable for initial expansion, CNS recruitment and differentiation of primary resident memory CD8 T cells as long as the duration of antigen exposure is limited. By contrast, CD4 T cells are essential to prolong primary CD8 T-cell function in the CNS and imprint memory CD8 T cells for recall responses. url: https://www.ncbi.nlm.nih.gov/pubmed/25187405/ doi: 10.1111/imm.12378 id: cord-328763-hcbs20a0 author: Ifergan, Igal title: Potential for Targeting Myeloid Cells in Controlling CNS Inflammation date: 2020-10-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Multiple Sclerosis (MS) is characterized by immune cell infiltration to the central nervous system (CNS) as well as loss of myelin. Characterization of the cells in lesions of MS patients revealed an important accumulation of myeloid cells such as macrophages and dendritic cells (DCs). Data from the experimental autoimmune encephalomyelitis (EAE) model of MS supports the importance of peripheral myeloid cells in the disease pathology. However, the majority of MS therapies focus on lymphocytes. As we will discuss in this review, multiple strategies are now in place to target myeloid cells in clinical trials. These strategies have emerged from data in both human and mouse studies. We discuss strategies targeting myeloid cell migration, growth factors and cytokines, biological functions (with a focus on miRNAs), and immunological activities (with a focus on nanoparticles). url: https://www.ncbi.nlm.nih.gov/pubmed/33123148/ doi: 10.3389/fimmu.2020.571897 id: cord-004911-fbge8tkc author: Imrich, H. title: On the role of peripheral macrophages during active experimental allergic encephalomyelitis (EAE) date: 2001 words: 6033.0 sentences: 356.0 pages: flesch: 51.0 cache: ./cache/cord-004911-fbge8tkc.txt txt: ./txt/cord-004911-fbge8tkc.txt summary: Severely and mildly diseased animals were analysed with respect to infiltration of T-cells, macrophages and upregulation of MHC class II molecules on microglia in the brain. Experimental allergic encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS) inducible in susceptible strains of rats by active immunisation with myelin basic protein (MBP) in adjuvant. To monitor such differences between diseased animals and animals without symptoms, leukocytes were isolated from the CNS and analysed by flow cytometry with regard to infiltrating T-cells (TCRϩ), macrophages (CD45 high ) and activation of resident microglia (CD45 low , MHC IIϩ). After immunisation of rats with MBP in CFA containing high dose of myc.T animals develop severe disease with high influx of T-cells and peripheral macrophages in brain tissue. After immunisation of rats with CFA containing low dose of myc.T, and constant concentrations of the autoantigen MBP animals failed to develop severe symptoms, nevertheless, they showed strong T-cell influx in brain parenchyma. abstract: Experimental allergic encephalitis (EAE) is an experimental autoimmune inflammatory condition of the central nervous system (CNS) that serves as a disease model for multiple sclerosis (MS). The primary effector mechanisms of the immune system leading to tissue destruction during EAE remain still controversial. T-cells, microglia, and macrophages infiltrating the brain parenchyma are suggested to be involved. To clarify the role of these cells during disease Lewis rats were immunised with different immunisation protocols: Immunisation with myelin basic protein (MBP) in complete Freunds adjuvant (CFA) containing high dose of mycobacterial components induced severe disease, whereas immunisation with low dose of mycobacterial components induced only mild disease. Severely and mildly diseased animals were analysed with respect to infiltration of T-cells, macrophages and upregulation of MHC class II molecules on microglia in the brain. All immunised rats showed high T-cell infiltration accompanied by microglia activation. The degree of disease and the infiltration of macrophages varied with dose of adjuvant. Lowering the dose of adjuvant prevented the development of disease but also the influx of peripheral macrophages into the brain without affecting the peripheral T-cell response to the autoantigen. Thus, appearance of (autoreactive) T-cells in the brain and microglia activation were probably not sufficient for development of disease. It can be concluded that peripheral macrophages play an essential or even key role in the pathogenesis of active EAE. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087617/ doi: 10.1007/s007020170060 id: cord-325624-6anybxnk author: Ireland, Derek D. C. title: RNase L Mediated Protection from Virus Induced Demyelination date: 2009-10-02 words: 8082.0 sentences: 397.0 pages: flesch: 43.0 cache: ./cache/cord-325624-6anybxnk.txt txt: ./txt/cord-325624-6anybxnk.txt summary: The unique phenotype of infected RL(−/−) mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. RNase L specifically protected the brain stem from sustained infection and prevented spread of virus to microglia/macrophages located in spinal cord grey matter. The increased pathological changes in both brain stem and spinal cord thus correlated with the high mortality rates of RL 2/2 mice starting at day 9 p.i. The inability to directly link increased axonal damage with enhanced neuronal infection remains puzzling and supports dysregulation of oligodendrocyte function and/or neuroprotective functions of microglia as contributing factors to the severe pathological phenotype and clinical outcome. Numerous functions of RNase L, not directly associated with anti-viral activity, may contribute to the increased susceptibility of RL 2/2 mice to MHV-JHM infection. abstract: IFN-α/β plays a critical role in limiting viral spread, restricting viral tropism and protecting mice from neurotropic coronavirus infection. However, the IFN-α/β dependent mechanisms underlying innate anti-viral functions within the CNS are poorly understood. The role of RNase L in viral encephalomyelitis was explored based on its functions in inhibiting translation, inducing apoptosis, and propagating the IFN-α/β pathway through RNA degradation intermediates. Infection of RNase L deficient (RL(−/−)) mice with a sub-lethal, demyelinating mouse hepatitis virus variant revealed that the majority of mice succumbed to infection by day 12 p.i. However, RNase L deficiency did not affect overall control of infectious virus, or diminish IFN-α/β expression in the CNS. Furthermore, increased morbidity and mortality could not be attributed to altered proinflammatory signals or composition of cells infiltrating the CNS. The unique phenotype of infected RL(−/−) mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. Increased tissue damage coincided with sustained brain stem infection, foci of microglia infection in grey matter, and increased apoptotic cells. These data demonstrate a novel protective role for RNase L in viral induced CNS encephalomyelitis, which is not reflected in overall viral control or propagation of IFN-α/β mediated signals. Protective function is rather associated with cell type specific and regional restriction of viral replication in grey matter and ameliorated neurodegeneration and demyelination. url: https://www.ncbi.nlm.nih.gov/pubmed/19798426/ doi: 10.1371/journal.ppat.1000602 id: cord-298847-szezd2vb author: Jacomy, Hélène title: Vacuolating encephalitis in mice infected by human coronavirus OC43 date: 2003-10-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Involvement of viruses in human neurodegenerative diseases and the underlying pathologic mechanisms remain generally unclear. Human respiratory coronaviruses (HCoV) can infect neural cells, persist in human brain, and activate myelin-reactive T cells. As a means of understanding the human infection, we characterized in vivo the neurotropic and neuroinvasive properties of HCoV-OC43 through the development of an experimental animal model. Virus inoculation of 21-day postnatal C57BL/6 and BALB/c mice led to a generalized infection of the whole CNS, demonstrating HCoV-OC43 neuroinvasiveness and neurovirulence. This acute infection targeted neurons, which underwent vacuolation and degeneration while infected regions presented strong microglial reactivity and inflammatory reactions. Damage to the CNS was not immunologically mediated and microglial reactivity was instead a consequence of direct virus-mediated neuronal injury. Although this acute encephalitis appears generally similar to that induced by murine coronaviruses, an important difference rests in the prominent spongiform-like degeneration that could trigger neuropathology in surviving animals. url: https://www.ncbi.nlm.nih.gov/pubmed/14592756/ doi: 10.1016/s0042-6822(03)00323-4 id: cord-295041-5vpawtef author: Jakhmola, Shweta title: SARS-CoV-2, an Underestimated Pathogen of the Nervous System date: 2020-09-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Numerous clinical studies have reported neurological symptoms in COVID-19 patients since the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), apart from the atypical signs of pneumonia. Angiotensin-converting enzyme-2 (ACE-2), a potential receptor for SARS-CoV-2 entry, is expressed on various brain cells and cerebral parts, i.e., subfornical organ, paraventricular nucleus, nucleus of the tractus solitarius, and rostral ventrolateral medulla, as well as in non-cardiovascular areas such as the motor cortex and raphe. The resident CNS cells like astrocytes and microglia also express ACE-2, thus highlighting the vulnerability of the nervous system to SARS-CoV-2 infection. Additionally, transmembrane serine protease 2 (TMPRSS2) and furin facilitate virus entry into the host. Besides, the probable routes of virus entry into the nervous system include the hematogenic pathway, through the vagus, the olfactory nerve, or the enteric nervous system. However, the trajectory of SARS-CoV-2 to the brain needs investigation. Furthermore, a Th17-mediated cytokine storm is seen in COVID-19 cases with higher levels of IL-1β/2/7/8/9/10/17, GM-CSF, IFN-γ, TNF-α, CXCL-10, MCP1, and MIP1α/β. Some cytokines can cross the blood-brain barrier and activate the brain’s immune cells to produce neural cytokines, leading to neuronal dysfunctions. Nonetheless, most of the neurological conditions developed due to viral infections may not have effective and registered treatments. Although, some antivirals may inhibit the virus-mediated pathogenesis and prove to be suitable in COVID-19 treatment. Therefore, clinicians’ and researchers’ collective expertise may unravel the potential of SARS-CoV-2 infection to prevent short-term and long-term CNS damage. url: https://doi.org/10.1007/s42399-020-00522-7 doi: 10.1007/s42399-020-00522-7 id: cord-021500-sy6lnt7b author: Jean Harry, G. title: Myelination, Dysmyelination, and Demyelination date: 2007-05-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150038/ doi: 10.1016/b978-012648860-9.50007-8 id: cord-284038-93s3ffoy author: Keyhanian, Kiandokht title: SARS-CoV-2 and nervous system: From pathogenesis to clinical manifestation date: 2020-11-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Since the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a growing body of evidence indicates that besides common COVID-19 symptoms, patients may develop various neurological manifestations affecting both the central and peripheral nervous systems as well as skeletal muscles. These manifestations can occur prior, during and even after the onset of COVID-19 general symptoms. In this Review, we discuss the possible neuroimmunological mechanisms underlying the nervous system and skeletal muscle involvement, and viral triggered neuroimmunological conditions associated with SARS-CoV-2, as well as therapeutic approaches that have been considered for these specific complications worldwide. url: https://www.sciencedirect.com/science/article/pii/S0165572820306974?v=s5 doi: 10.1016/j.jneuroim.2020.577436 id: cord-277679-sc9hugxr author: Khateb, Mohamed title: Coronaviruses and Central Nervous System Manifestations date: 2020-06-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: SARS-CoV-2 is a highly pathogenic coronavirus that has caused an ongoing worldwide pandemic. Emerging in Wuhan, China in December 2019, the virus has spread rapidly around the world. Corona virus disease 2019 (COVID-19), which is caused by SARS-CoV-2, has resulted in significant morbidity and mortality. The most prominent symptoms of SARS-CoV-2 infection are respiratory. However, accumulating evidence highlights involvement of the central nervous system (CNS). This includes headache, anosmia, meningoencephalitis, acute ischemic stroke, and several presumably post/para-infectious syndromes and altered mental status not explained by respiratory etiologies. Interestingly, previous studies in animal models emphasized the neurotropism of coronaviruses; thus, these CNS manifestations of COVID-19 are not surprising. This minireview scans the literature regarding the involvement of the CNS in coronavirus infections in general, and in regard to the recent SARS-CoV-2, specifically. url: https://www.ncbi.nlm.nih.gov/pubmed/32655490/ doi: 10.3389/fneur.2020.00715 id: cord-269861-r07osd0w author: Kim, Jin Hyoung title: CCR5 ameliorates Japanese encephalitis via dictating the equilibrium of regulatory CD4(+)Foxp3(+) T and IL-17(+)CD4(+) Th17 cells date: 2016-07-20 words: 12067.0 sentences: 720.0 pages: flesch: 60.0 cache: ./cache/cord-269861-r07osd0w.txt txt: ./txt/cord-269861-r07osd0w.txt summary: Our results also revealed that adoptive transfer of sorted CCR5(+)CD4(+)Foxp3(+) Tregs into Ccr5(−/−) mice could ameliorate JE progression without apparently altering the viral burden and CNS infiltration of IL-17(+)CD4(+) Th17 cells, myeloid-derived Ly-6C(hi) monocytes and Ly-6G(hi) granulocytes. The frequency and absolute number of CD4 + Foxp3 + Tregs (a, c), IFN-γ + CD4 + Th1, and IL-17 + CD4 + Th17 cells (b, d) in the spleen (a, b) and brain (c, d) of Ccr5 +/+ and Ccr5 −/− mice were determined by flow cytometric analysis at 3 and 5 days following JEV (3.0 × 10 7 pfu) infection. Although our results suggest that the increased number of CD4 + Foxp3 + Tregs in extraneural lymphoid tissue and the CNS of Ccr5 +/+ mice is associated with mild JE, we did not provide direct evidence regarding whether the enhanced response of CD4 + Foxp3 + Tregs plays a beneficial role in JE progression. abstract: BACKGROUND: CCR5 is a CC chemokine receptor involved in the migration of effector leukocytes including macrophages, NK, and T cells into inflamed tissues. Also, the role of CCR5 in CD4(+)Foxp3(+) regulatory T cell (Treg) homing has recently begun to grab attention. Japanese encephalitis (JE) is defined as severe neuroinflammation of the central nervous system (CNS) following infection with mosquito-borne flavivirus JE virus. However, the potential contribution of CCR5 to JE progression via mediating CD4(+)Foxp3(+) Treg homing has not been investigated. METHODS: Infected wild-type (Ccr5(+/+)) and CCR5-deficient (Ccr5(−/−)) mice were examined daily for mortality and clinical signs, and neuroinflammation in the CNS was evaluated by infiltration of inflammatory leukocytes and cytokine expression. In addition, viral burden, NK- and JEV-specific T cell responses were analyzed. Adoptive transfer of CCR5(+)CD4(+)Foxp3(+) Tregs was used to evaluate the role of Tregs in JE progression. RESULTS: CCR5 ablation exacerbated JE without altering viral burden in the extraneural and CNS tissues, as manifested by increased CNS infiltration of Ly-6C(hi) monocytes and Ly-6G(hi) granulocytes. Compared to Ccr5(+/+) mice, Ccr5(−/−) mice unexpectedly showed increased responses of IFN-γ(+)NK and CD8(+) T cells in the spleen, but not CD4(+) T cells. More interestingly, CCR5-ablation resulted in a skewed response to IL-17(+)CD4(+) Th17 cells and correspondingly reduced CD4(+)Foxp3(+) Tregs in the spleen and brain, which was closely associated with exacerbated JE. Our results also revealed that adoptive transfer of sorted CCR5(+)CD4(+)Foxp3(+) Tregs into Ccr5(−/−) mice could ameliorate JE progression without apparently altering the viral burden and CNS infiltration of IL-17(+)CD4(+) Th17 cells, myeloid-derived Ly-6C(hi) monocytes and Ly-6G(hi) granulocytes. Instead, adoptive transfer of CCR5(+)CD4(+)Foxp3(+) Tregs into Ccr5(−/−) mice resulted in increased expression of anti-inflammatory cytokines (IL-10 and TGF-β) in the spleen and brain, and transferred CCR5(+) Tregs were found to produce IL-10. CONCLUSIONS: CCR5 regulates JE progression via governing timely and appropriate CNS infiltration of CD4(+)Foxp3(+) Tregs, thereby facilitating host survival. Therefore, this critical and extended role of CCR5 in JE raises possible safety concerns regarding the use of CCR5 antagonists in human immunodeficiency virus (HIV)-infected individuals who inhabit regions in which both HIV and flaviviruses, such as JEV and West Nile virus, are endemic. url: https://www.ncbi.nlm.nih.gov/pubmed/27439902/ doi: 10.1186/s12974-016-0656-x id: cord-002021-67ao8chx author: Kim, Seong Bum title: Blockage of indoleamine 2,3-dioxygenase regulates Japanese encephalitis via enhancement of type I/II IFN innate and adaptive T-cell responses date: 2016-04-18 words: 12049.0 sentences: 601.0 pages: flesch: 51.0 cache: ./cache/cord-002021-67ao8chx.txt txt: ./txt/cord-002021-67ao8chx.txt summary: Because viral loads at the periphery in IDO-ablated mice were lower than in wild-type BL/6 mice, we evaluated the contribution of DC subsets (conventional and plasmacytoid) and macrophages to the IFN-I innate immune responses caused by JEV infection in the IDOablated environment. IDO-ablated BMDCs and pDCs, but not BMDMs, showed rapid induction of IFN-α/β in response to JEV infection compared to levels measured in cells from wild-type BL/6 mice. Collectively, IDO ablation appears to provide rapid and increased responses of IFN-I innate immunity in myeloid-derived DCs and pDCs upon JEV infection, thereby contributing to the amelioration of JE through early control of viral replication. Therefore, we examined viral replication and IFN-I innate immune responses in primary cortical neuron cells generated from wild-type BL/6 and IDO-ablated mice after JEV infection. abstract: BACKGROUND: Japanese encephalitis (JE), a leading cause of viral encephalitis, is characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV). Indoleamine 2,3-dioxygenase (IDO) has been identified as an enzyme associated with immunoregulatory function. Although the regulatory role of IDO in viral replication has been postulated, the in vivo role of IDO activity has not been fully addressed in neurotropic virus-caused encephalitis. METHODS: Mice in which IDO activity was inhibited by genetic ablation or using a specific inhibitor were examined for mortality and clinical signs after infection. Neuroinflammation was evaluated by central nervous system (CNS) infiltration of leukocytes and cytokine expression. IDO expression, viral burden, JEV-specific T-cell, and type I/II interferon (IFN-I/II) innate responses were also analyzed. RESULTS: Elevated expression of IDO activity in myeloid and neuron cells of the lymphoid and CNS tissues was closely associated with clinical signs of JE. Furthermore, inhibition of IDO activity enhanced resistance to JE, reduced the viral burden in lymphoid and CNS tissues, and resulted in early and increased CNS infiltration by Ly-6C(hi) monocytes, NK, CD4(+), and CD8(+) T-cells. JE amelioration in IDO-ablated mice was also associated with enhanced NK and JEV-specific T-cell responses. More interestingly, IDO ablation induced rapid enhancement of type I IFN (IFN-I) innate responses in CD11c(+) dendritic cells (DCs), including conventional and plasmacytoid DCs, following JEV infection. This enhanced IFN-I innate response in IDO-ablated CD11c(+) DCs was coupled with strong induction of PRRs (RIG-I, MDA5), transcription factors (IRF7, STAT1), and antiviral ISG genes (Mx1, Mx2, ISG49, ISG54, ISG56). IDO ablation also enhanced the IFN-I innate response in neuron cells, which may delay the spread of virus in the CNS. Finally, we identified that IDO ablation in myeloid cells derived from hematopoietic stem cells (HSCs) dominantly contributed to JE amelioration and that HSC-derived leukocytes played a key role in the enhanced IFN-I innate responses in the IDO-ablated environment. CONCLUSIONS: Inhibition of IDO activity ameliorated JE via enhancement of antiviral IFN-I/II innate and adaptive T-cell responses and increased CNS infiltration of peripheral leukocytes. Therefore, our data provide valuable insight into the use of IDO inhibition by specific inhibitors as a promising tool for therapeutic and prophylactic strategies against viral encephalitis caused by neurotropic viruses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4835894/ doi: 10.1186/s12974-016-0551-5 id: cord-349285-zmp7sw5q author: Koh, Kyung‐Nam title: Clinical features, genetics, and outcome of pediatric patients with hemophagocytic lymphohistiocytosis in Korea: report of a nationwide survey from Korea Histiocytosis Working Party date: 2014-07-03 words: 3939.0 sentences: 220.0 pages: flesch: 43.0 cache: ./cache/cord-349285-zmp7sw5q.txt txt: ./txt/cord-349285-zmp7sw5q.txt summary: BACKGROUND: We analyzed a nationwide registry of pediatric patients with hemophagocytic lymphohistiocytosis (HLH) in Korea to assess the clinical and genetic features and treatment outcomes in pediatric HLH. CONCLUSION: Our study showed the unique predominance of a UNC13D mutation and vulnerability to Epstein–Barr virus infection in Korean children with HLH and emphasizes the prognostic significance of age, liver dysfunction, and treatment responses in this disease. The case report form included information on demographic characteristics, clinical, laboratory, and radiological findings at presentation, genetic mutation analysis, type of treatment and responses to treatment, allogeneic hematopoietic stem cell transplantation, and survival outcomes. In the familial HLH group, only a coagulation abnormality was a marginally significant prognostic factor, and CNS involvement and age were not found to be significantly associated with survival outcome. CNS involvement was found to be a significant prognostic factor in our presumed secondary HLH group but was not associated with a poor outcome in the familial group. abstract: BACKGROUND: We analyzed a nationwide registry of pediatric patients with hemophagocytic lymphohistiocytosis (HLH) in Korea to assess the clinical and genetic features and treatment outcomes in pediatric HLH. METHODS: The Korea Histiocytosis Working Party retrospectively analyzed data on 251 pediatric patients diagnosed with HLH between 1996 and 2011. RESULTS: In the study cohort, 25 cases were categorized with familial HLH, 64 with presumed secondary HLH, and 162 with unspecified HLH. Of 217 evaluable patients, 91 (42%) had concomitant Epstein–Barr virus infection. Of 238 evaluable patients, central nervous system (CNS) involvement, which was more frequent in the familial group, was evident in 81 cases (34%). Genetic tests revealed a predominant UNC13D mutation with a high incidence of two recurrent splicing mutations (c.118‐308C>T and c.754‐1G>C). The 5‐yr overall survival rate was 68% (38% in the familial group and 81% in the presumed secondary group). The 5‐yr overall survival rate among 32 patients who underwent allogeneic hematopoietic stem cell transplantation was 64%. In multivariate analysis, a younger age at diagnosis, severe transaminasemia, and a coagulation abnormality were independent prognostic factors for survival. Responses during initial treatments were also significant indicators of outcome. CONCLUSION: Our study showed the unique predominance of a UNC13D mutation and vulnerability to Epstein–Barr virus infection in Korean children with HLH and emphasizes the prognostic significance of age, liver dysfunction, and treatment responses in this disease. A multicenter prospective trial that builds on the present results is warranted to identify subgroups of patients with a poor prognosis and identify optimal treatments. url: https://www.ncbi.nlm.nih.gov/pubmed/24935083/ doi: 10.1111/ejh.12399 id: cord-030371-wp6xmaqe author: Kubota, Kazuo title: Basic Science of PET Imaging for Inflammatory Diseases date: 2019-12-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: FDG-PET/CT has recently emerged as a useful tool for the evaluation of inflammatory diseases too, in addition to that of malignant diseases. The imaging is based on active glucose utilization by inflammatory tissue. Autoradiography studies have demonstrated high FDG uptake in macrophages, granulocytes, fibroblasts, and granulation tissue. Especially, activated macrophages are responsible for the elevated FDG uptake in some types of inflammation. According to one study, after activation by lipopolysaccharide of cultured macrophages, the [(14)C]2DG uptake by the cells doubled, reaching the level seen in glioblastoma cells. In activated macrophages, increase in the expression of total GLUT1 and redistributions from the intracellular compartments toward the cell surface have been reported. In one rheumatoid arthritis model, following stimulation by hypoxia or TNF-α, the highest elevation of the [(3)H]FDG uptake was observed in the fibroblasts, followed by that in macrophages and neutrophils. As the fundamental mechanism of elevated glucose uptake in both cancer cells and inflammatory cells, activation of glucose metabolism as an adaptive response to a hypoxic environment has been reported, with transcription factor HIF-1α playing a key role. Inflammatory cells and cancer cells seem to share the same molecular mechanism of elevated glucose metabolism, lending support to the notion of usefulness of FDGPET/CT for the evaluation of inflammatory diseases, besides cancer. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418531/ doi: 10.1007/978-981-15-0810-3_1 id: cord-252389-xrdbmosj author: Kumar, Mukesh title: Neurological manifestations and comorbidity associated with COVID-19: an overview date: 2020-10-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: First in 2002, severe acute respiratory syndrome coronavirus (SARS-CoV), second in 2012, Middle East respiratory syndrome coronavirus (MERS-CoV), and now the third in the December 2019, emergence of tremendously pathogenic and large-scale epidemic novel coronavirus (SARS-CoV-2) has brought the worst conditions into the human inhabitants of the twenty-first century. The SARS-CoV-2 uses the resembling receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly feasts through the respiratory tract. The ACE2 receptor appearances have been also detected upon glial cells and neurons, which makes them a potential target of SARS-CoV-2 disease (COVID-19). Consequently, cells expressing ACE2, apart from lung and cardiovascular tissue, neurons and glial cells may act as targets and are thus vulnerable to SARS-CoV-2 systemic infection as well as its central nervous system (CNS) comorbidities. Investigation of the neurological manifestations of COVID-19 is a step towards better understanding the SARS-CoV-2 infections, inhibiting the additional spread and treating patients affected by this pandemic. In this concern, more clinical examinations for CNS involvement of SARS-CoV-2 are warranted. In this article, we have reviewed the neurological characteristic features of COVID-19 patients, latent neurotropic mechanisms of SARS-CoV-2 involvement in the comorbidity associated with CNS disorders, and neurological manifestations associated with COVID-19. Therefore, in the perspective of COVID-19 pandemic, clinicians and healthcare workers should be aware of a wide spectrum of neurological manifestations associated with COVID-19 along with their signs and symptoms for initial diagnosis and isolation of the patients. url: https://doi.org/10.1007/s10072-020-04823-6 doi: 10.1007/s10072-020-04823-6 id: cord-002209-xs6qigg4 author: Kıray, Hülya title: The multifaceted role of astrocytes in regulating myelination date: 2016-09-17 words: 7509.0 sentences: 355.0 pages: flesch: 35.0 cache: ./cache/cord-002209-xs6qigg4.txt txt: ./txt/cord-002209-xs6qigg4.txt summary: In experimental allergic encephalomyelitis (EAE), a widely used animal model of MS, where demyelination is induced by myelin antigens, administered together with adjuvant that contains bacterial components (Traugott and Lebon, 1988; Tsukada et al., 1991; Villarroya et al., 1996) , GFAP expression was seen on more numerous and much larger astrocytic processes in chronic lesions compared to normal appearing white matter (Webster et al., 1985; Eng et al., 1971) . The milder "activated" astrocytes can secrete a range of factors including; neurotrophic factors, growth factors, and cytokines that will stimulate re/myelination by promoting neuronal survival, neurite outgrowth, neurogenesis, and/ or oligodendrocyte precursor cell (OPC) survival, proliferation, and/or maturation. Conversely astrocytes that tend to have a more severe "reactive" phenotype, possibly induced by proinflammatory cytokines/CNS tissue damage, may secrete cytokines and chemokines that lead to myelin and oligodendrocyte damage in vitro, suppress remyelination, delay disease recovery in experimental autoimmune encephalomyelitis (EAE), and suppress myelination in myelinating embryonic rat mixed spinal cord cultures. Transplantation of ciliary neurotrophic factor-expressing adult oligodendrocyte precursor cells promotes remyelination and functional recovery after spinal cord injury abstract: Astrocytes are the major glial cell of the central nervous system (CNS), providing both metabolic and physical support to other neural cells. After injury, astrocytes become reactive and express a continuum of phenotypes which may be supportive or inhibitory to CNS repair. This review will focus on the ability of astrocytes to influence myelination in the context of specific secreted factors, cytokines and other neural cell targets within the CNS. In particular, we focus on how astrocytes provide energy and cholesterol to neurons, influence synaptogenesis, affect oligodendrocyte biology and instigate cross-talk between the many cellular components of the CNS. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019113/ doi: 10.1016/j.expneurol.2016.03.009 id: cord-028963-u4iupl1s author: Lane, Michael title: Multiple Sclerosis date: 2020-07-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348625/ doi: 10.1016/b978-0-323-43044-9.00199-0 id: cord-349135-it5ahzj3 author: Lane, T. E. title: Functional Diversity of Chemokines and Chemokine Receptors in Response to Viral Infection of the Central Nervous System date: 2006 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Encounters with neurotropic viruses result in varied outcomes ranging from encephalitis, paralytic poliomyelitis or other serious consequences to relatively benign infection. One of the principal factors that control the outcome of infection is the localized tissue response and subsequent immune response directed against the invading toxic agent. It is the role of the immune system to contain and control the spread of virus infection in the central nervous system (CNS), and paradoxically, this response may also be pathologic. Chemokines are potent proinflammatory molecules whose expression within virally infected tissues is often associated with protection and/or pathology which correlates with migration and accumulation of immune cells. Indeed, studies with a neurotropic murine coronavirus, mouse hepatitis virus (MHV), have provided important insight into the functional roles of chemokines and chemokine receptors in participating in various aspects of host defense as well as disease development within the CNS. This chapter will highlight recent discoveries that have provided insight into the diverse biologic roles of chemokines and their receptors in coordinating immune responses following viral infection of the CNS. url: https://www.ncbi.nlm.nih.gov/pubmed/16570854/ doi: 10.1007/978-3-540-33397-5_1 id: cord-021772-5v4gor2v author: Levine, Gwendolyn J. title: Cerebrospinal Fluid and Central Nervous System Cytology date: 2019-05-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151995/ doi: 10.1016/b978-0-323-53314-0.00014-6 id: cord-268835-catuja6c author: Libbey, Jane E. title: Molecular Mimicry in Multiple Sclerosis date: 2007-12-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: One of the most common demyelinating central nervous system (CNS) diseases in humans is multiple sclerosis (MS). The disease can be very debilitating with vision loss, motor and sensory disturbances, and cognitive impairment. The clinical course may present as a relapsing‐remitting disease course, a progressive disease course, or a combination thereof. The etiology of MS is unknown. Though many viruses have been shown to be associated with MS, no one virus has ever been demonstrated to be the cause of MS. In addition, MS is thought to have an autoimmune component. Molecular mimicry is one hypothesis put forth which could reconcile the diverse pathology and etiology of MS. Molecular mimicry occurs when peptides from pathogens share sequence or structural similarities with self‐antigens. Infection with various pathogens, each with its individual molecular mimic to a CNS antigen, may explain the inability of investigators to link one specific virus to MS. Molecular mimicry may be mediated through human leukocyte antigen class I‐ and class II‐restricted T cells and antibodies, which may explain the diversity in phenotype. Aspects of molecular mimicry will be discussed in relation to each of these immune system components. Examples of various molecular mimics will be discussed with a particular focus on the CNS and MS. Molecular mimicry alone may not be able to induce disease; priming of the immune system by infection with a pathogen that carries a molecular mimic to self may have to be followed by a later nonspecific immunologic challenge in order for disease to be initiated. Recent research into this priming and triggering of disease will be discussed in relation to an animal model for MS. url: https://www.sciencedirect.com/science/article/pii/S0074774207790062 doi: 10.1016/s0074-7742(07)79006-2 id: cord-008586-5jinvuyn author: Loihl, Angela K. title: Chapter 18 Expression of nitric oxide synthase-2 in glia associated with CNS pathology date: 2008-04-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: This chapter discusses the expression of nitric oxide synthase-2 (NOS-2) in glia associated with central nervous system (CNS) pathology. The production of nitric oxide (NO) in the nervous system is catalyzed by three, highly homologous isoforms of NO synthase (NOS). NOS-2, the dimeric, heme-containing, soluble protein whose activity is independent of a rise in intracellular calcium, is variously termed ‘inducible,’ ‘immunologic,’ and ‘macrophage NOS (macNOS).’ Nitric oxide inhibits not only NOS-2 activity but also regulates the level of NOS-2 messenger RNA (mRNA) expression through a mechanism involving NF-(K) B. There is specific evidence for the glial expression of NOS-2 associated with neuronal injury and infection of the CNS and in neurodegenerative and demyelinating diseases. Direct injury in the CNS results in a reactive gliosis, characterized by the induction of the glial fibrillary acidic protein gene and changes in astrocyte morphology. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133158/ doi: 10.1016/s0079-6123(08)63213-6 id: cord-311845-wnk7itha author: Lubetzki, Catherine title: Demyelination in multiple sclerosis date: 2014-02-05 words: 7400.0 sentences: 345.0 pages: flesch: 37.0 cache: ./cache/cord-311845-wnk7itha.txt txt: ./txt/cord-311845-wnk7itha.txt summary: Whereas multiple sclerosis was long considered as a T cell-mediated disease, the role of B lymphocytes is now increasingly recognized, and the influence of antibodies on tissue damage actively investigated. Multiple sclerosis (MS) is generally considered as an autoimmune disease, in which autoreactive T cells enter the central nervous system (CNS) from the peripheral circulation and induce an inflammatory cascade resulting in demyelination and axonal loss. Nevertheless, vesicular disruption of myelin seen in highly active MS lesions was found to be associated with anti-MOG and MBP antibodies, suggesting that demyelination might be causally related to the deposition of antigen-specific autoantibodies (Genain et al., 1999) . Recent findings have suggested that, following a primary oligodendrocyte or myelin injury, local APCs could process myelin antigens and traffic from the CNS to secondary lymphoid organs, where they may induce or enhance an adaptive demyelinating immune reaction. abstract: This review, focused on demyelination in multiple sclerosis, is divided in two parts. The first part addresses the many and not exclusive mechanisms leading to demyelination in the central nervous system. Although the hypothesis that a primary oligodendrocyte or myelin injury induces a secondary immune response in the central nervous system is still a matter of debate, most recent advances underline the influence of a primary immune response against myelin antigen(s), with a diversity of potential targets. Whereas multiple sclerosis was long considered as a T cell-mediated disease, the role of B lymphocytes is now increasingly recognized, and the influence of antibodies on tissue damage actively investigated. The second part of the review describes the axonal consequences of demyelination. Segmental demyelination results in conduction block or slowing of conduction through adaptative responses, notably related to modifications in the distribution of voltage gated sodium channels along the denuded axon. If demyelination persists, these changes, as well as the loss of trophic and metabolic support, will lead to irreversible axonal damage and loss. In this respect, favouring early myelin repair, during a window of time when axonal damage is still reversible, might pave the way for neuroprotection. url: https://www.sciencedirect.com/science/article/pii/B9780444520012000042 doi: 10.1016/b978-0-444-52001-2.00004-2 id: cord-264794-bgygebgx author: Lundgren, A.-L. title: Feline non-suppurative meningoencephalomyelitis. A clinical and pathological study date: 1992-11-30 words: 4861.0 sentences: 288.0 pages: flesch: 48.0 cache: ./cache/cord-264794-bgygebgx.txt txt: ./txt/cord-264794-bgygebgx.txt summary: It has been argued that the syndrome may include several aetiologically unrelated conditions affecting the central nervous system of cats, e.g. toxoplasmosis (Hirth and Nielsen, 1969) and the cerebral form of feline infectious peritonitis (Slauson and Finn, 1972; Kornegay, 1978) . Histopathological examination revealed throughout the central nervous system a non-suppurative inflammation characterized by perivascular mononuclear cuffing, presence of inflammatory nodules and neuronal degeneration in all cats. Neuropathological examination of the cats of the present study showed a marked inflammatory reaction in the cerebral leptomeninges as well as in the grey matter of the brain and spinal cord. Neither the serological results nor the clinical and histopathological findings in the cats with staggering disease indicate a FeLV infection. Feline immunodeficiency virus (FIV) has emerged as an important cause of neurological disease in cats (Dow, Poss and Hoover, 1990; Sparger, 1991) , often in association with clinical syndromes typical of an immunodeficient state (chronic stomatitis, enteritis, dermatitis, etc). abstract: Abstract A spontaneous neurological disease in cats characterized by behavioural and motor disturbances was investigated by clinical, morphological and immunological methods. Neuropathological examination showed a marked inflammatory reaction in the cerebral leptomeninges and the grey matter of the brain. In the white matter, the reaction was moderate. The changes consisted of perivascular cuffing by mononuclear cells and neuronal damage. The brain stem (thalamus, mesencephalon, caudal colliculus) was most severely affected. The spinal cord and its leptomeninges were involved to a lesser degree. The histopathological picture as well as the laboratory findings suggests a viral cause of the disease. The morphology of the disease and serological as well as immunohistochemical results indicate that this disorder is different from previously known feline viral encephalitides. url: https://www.sciencedirect.com/science/article/pii/002199759290015M doi: 10.1016/0021-9975(92)90015-m id: cord-331268-kzy33hdb author: Lynch, Sharon G. title: Multiple sclerosis date: 1996-01-31 words: 13844.0 sentences: 885.0 pages: flesch: 47.0 cache: ./cache/cord-331268-kzy33hdb.txt txt: ./txt/cord-331268-kzy33hdb.txt summary: Abnormalities in the cerebral hemispheres are frequently periventricular in distribution and only occasionally correlate with specific symptoms or signs.6,7 The accumulation of lesions in the frontal lobes is associated with a decline in memory.8 In addition, a change in the number of lesions on cranial MR images correlates with a change in overall clinical status as measured with standard scales.g Observations made with MRI are having a marked impact on both our basic knowledge of MS and on therapeutic trialsJo MRI studies will provide considerable insight into the natural history of the disease and will be an excellent independent variable in future clinical trials. Signs and symptoms that commonly occur as MS progresses include vertigo, tremor, incoordination, increasing spasticity, depression, mood swings, cognitive abnormalities, impotence or other sexual dysfunction, weakness, Lhermitte''s sign, gait abnormalities, constipation, urinary incontinence, optic nerve pallor, fatigue, quadriparesis, dysarthria, loss of upper extremity coordination, and dysesthetic pain (Table 1) . abstract: Abstract Multiple sclerosis is a chronic disease that begins in late adolescence or adulthood. It is highly variable in its expression and severity. It is believed to be autoimmune in nature. The cause is unknown; both genetic and environmental factors have been implicated in the pathogenesis. MS generally presents with the acute or subacute onset of neurologic abnormalities that may wax and wane over many years. Diagnosis is generally made by means of observation of the clinical course in conjunction with a neurologic examination and laboratory tests. These tests may include magnetic resonance imaging of the head and spine, lumbar puncture, and evoked potentials. Treatment is based on general supportive care, the use of corticosteroids for relapses, and symptomatic management of ongoing problems. The frequency of relapses can be reduced with interferon-β (Betaseron). Copolymer 1 and interferon-β la are being evaluated by the U.S. Food and Drug Administration for approval for use for reduction in the frequency of relapses in relapsing-remitting MS. Treatment of chronic progression is often attempted with immunosuppressive agents such as corticosteroids, azathioprine, and cyclophosphamide. Use of other agents is being investigated. url: https://www.sciencedirect.com/science/article/pii/S0011502996900127 doi: 10.1016/s0011-5029(96)90012-7 id: cord-334577-wb6zhovi author: Mangale, Vrushali title: Microglia influence host defense, disease, and repair following murine coronavirus infection of the central nervous system date: 2020-05-25 words: 5118.0 sentences: 245.0 pages: flesch: 43.0 cache: ./cache/cord-334577-wb6zhovi.txt txt: ./txt/cord-334577-wb6zhovi.txt summary: Treatment with PLX5622, an inhibitor of colony stimulating factor 1 receptor (CSF1R) that efficiently depletes microglia, prior to infection of the central nervous system (CNS) with the neurotropic JHM strain of mouse hepatitis virus (JHMV) resulted in increased mortality compared with control mice that correlated with impaired control of viral replication. tor 1 receptor (CSF1R) that efficiently depletes microglia, prior to infection of the central nervous system (CNS) with the neurotropic JHM strain of mouse hepatitis virus (JHMV) resulted in increased mortality compared with control mice that correlated with impaired control of viral replication. Our findings emphasize an important role for microglia in aiding in host defense in response to JHMV infection of the CNS as well as influencing both the severity of spinal cord demyelination and remyelination in a model of murine coronavirus-induced neurologic disease. abstract: The present study examines functional contributions of microglia in host defense, demyelination, and remyelination following infection of susceptible mice with a neurotropic coronavirus. Treatment with PLX5622, an inhibitor of colony stimulating factor 1 receptor (CSF1R) that efficiently depletes microglia, prior to infection of the central nervous system (CNS) with the neurotropic JHM strain of mouse hepatitis virus (JHMV) resulted in increased mortality compared with control mice that correlated with impaired control of viral replication. Single cell RNA sequencing (scRNASeq) of CD45+ cells isolated from the CNS revealed that PLX5622 treatment resulted in muted CD4+ T cell activation profile that was associated with decreased expression of transcripts encoding MHC class II and CD86 in macrophages but not dendritic cells. Evaluation of spinal cord demyelination revealed a marked increase in white matter damage in PLX5622‐treated mice that corresponded with elevated expression of transcripts encoding disease‐associated proteins Osteopontin (Spp1), Apolipoprotein E (Apoe), and Triggering receptor expressed on myeloid cells 2 (Trem2) that were enriched within macrophages. In addition, PLX5622 treatment dampened expression of Cystatin F (Cst7), Insulin growth factor 1 (Igf1), and lipoprotein lipase (Lpl) within macrophage populations which have been implicated in promoting repair of damaged nerve tissue and this was associated with impaired remyelination. Collectively, these findings argue that microglia tailor the CNS microenvironment to enhance control of coronavirus replication as well as dampen the severity of demyelination and influence repair. url: https://doi.org/10.1002/glia.23844 doi: 10.1002/glia.23844 id: cord-271396-bol1zpji author: Manglani, Monica title: New advances in CNS immunity against viral infection date: 2018-02-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The central nervous system (CNS) is an immunologically specialized organ where restrictive barrier structures protect the parenchyma from inflammation and infection. This protection is important in preventing damage to non-renewable resident cell populations, such as neurons, responsible for functions ranging from executive to autonomic. Despite these barriers, the CNS can be infected through several entry portals, giving rise to meningitis and encephalitis. Following infection, resident cells recruit peripherally derived immune cells to sites of viral infection. In this review, we discuss recent advances in immune recruitment and entry at barrier structures as well as current immunotherapeutic strategies for the treatment of persistent viral infections. url: https://www.ncbi.nlm.nih.gov/pubmed/29289900/ doi: 10.1016/j.coviro.2017.12.003 id: cord-017917-7aeh6quc author: Marten, Norman W. title: The Role of Metalloproteinases in Corona Virus Infection date: 2005 words: 3000.0 sentences: 148.0 pages: flesch: 38.0 cache: ./cache/cord-017917-7aeh6quc.txt txt: ./txt/cord-017917-7aeh6quc.txt summary: A number of MMPs and TIMPs have also been associated with the CNS inflammatory/demyelinating disease multiple sclerosis (MS) in humans (2,32) as well as its rodent model experimental autoimmune encephalitis (EAE) (10,38). The consistent association of MMP and TIMP expression with inflammatory demyelinating disease suggests that MMPs play either a direct or indirect role in promoting CNS pathology (2,27,32). However, subsequent analysis of individual cell populations sorted from infected brains indicated that MMP-9 gene expression is up regulated several fold among infiltrating inflammatory cells (Zhou, unpublished data) (Table 1) . Thus, MMP-9 from neutrophils is regulated at the level of degranulation as opposed to gene transcription and co-expression of TIMPs. These data suggest MMP-9 is likely released from both mononuclear and polymorphonuclear infiltrates during JHMV infection. Cell surface binding and activation of gelatinase A induced by expression of membrane-type-l-matrix metalloproteinase (MT1-MMP) abstract: Infection with neurotropic strains of mouse hepatitis virus (MHV) results in rapid leukocyte infiltration into the central nervous system (CNS). The inflammatory response controls virus replication but fails to mediate sterile clearance. The persistence of viral RNA and inflammatory cells within the CNS is associated with the development of ongoing demyelination. Matrix metalloproteinases (MMPs) are a family of proteases involved in degradation of the extracellular matrix (ECM). During inflammatory responses MMPs are thought to play a significant role in breaking down the basement membrane surrounding blood vessels as well as parenchymal ECM thereby facilitating leukocyte infiltration. MMPs have also been associated with activation of chemokines and perhaps more significantly the degradation of myelin proteins and generation of autoantigens. Recent examination of MMP expression during MHV infection suggests that MMP-3, -9 and -12 are involved in the inflammatory response. The proinflammatory effects of these MMPs are likely tempered by induction of tissue inhibiter of metalloproteinase-1 expression. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122609/ doi: 10.1007/0-387-25518-4_48 id: cord-309109-c5hajb6k author: Matthews, A. E. title: Murine hepatitis virus—A model for virus-induced CNS demyelination date: 2002 words: 6898.0 sentences: 335.0 pages: flesch: 50.0 cache: ./cache/cord-309109-c5hajb6k.txt txt: ./txt/cord-309109-c5hajb6k.txt summary: Although activated , MHV-speci c, CD8 C T cells transferred to infected mice can control viral replication, they are not suf cient to clear infectious virus from oligodendrocytes (Stohlman et al, 1998b) . Clearance of an MHV strain that primarily infects neurons is delayed in the absence of IFN-gamma, suggesting that it may affect viral control in other cell types as well without being absolutely required for clearance (Lane et al, 1997) . The contribution of humoral immunity to viral clearance and persistent infection in the CNS has been investigated using mice de cient in secreted antibodies or B cells Bergmann et al, 2001; Matthews et al, 2001) . These data suggest that T cells play a role in controlling viral titers, even before 5 d.p.i. Beta2-microglobulinde cient mice, which lack CD8 C T cells, have delayed clearance of virus from the liver . abstract: Most murine hepatitis virus (MHV) strains, as their name suggests, infect the liver. However, several murine strains are tropic for the central nervous system (CNS) and cause encephalitis with subsequent CNS demyelination. The CNS demyelination shares pathological similarities with human CNS demyelinating diseases such as multiple sclerosis (MS). These viruses are, therefore, used to study the role of the immune system in viral clearance from the CNS, in CNS demyelination, and in remyelination. Nevertheless, it is still unclear exactly how MHV induces demyelination and to what extent the immune system plays a role in this pathology. Here we review this field in the context of the immune response to MHV in the liver and the CNS focusing on studies that have been published in the past 5 years. url: https://www.ncbi.nlm.nih.gov/pubmed/11935460/ doi: 10.1080/13550280290049534 id: cord-276533-cxyndepl author: McFarland, Henry F. title: Multiple sclerosis: Possible immunological mechanisms date: 1989-01-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract Multiple sclerosis is the principal demyelinating disease of the central nervous system. Although the prevalence of the disease is moderately low, averaging about 40 cases per 100,000 people in high risk areas, it is a particularly devastating disease. It primarily affects young adults, is chronic, and has an unpredictable course. Most discouraging, the cause of the disease is not known and an effective treatment has not been identified. Recently, however, research has yielded some important findings concerning the etiology of MS. Much evidence now points to an immunological process as one of the major elements in the disease. It is also likely that an environmental influence, possibly an infectious process, may contribute to the disease. Finally, it is now certain that genetic makeup influences susceptibility to the disease. At present, the strongest evidence is for a polygenic effect, not the effect of a single gene or gene locus. This review will examine some of the possible immunologically mediated disease processes that could be involved in MS, especially those that could account for a role for infectious and genetic factors in the disease. url: https://www.ncbi.nlm.nih.gov/pubmed/2521315/ doi: 10.1016/0090-1229(89)90116-5 id: cord-266078-h53zpjab author: McGuckin Wuertz, Kathryn title: STING is required for host defense against neuropathological West Nile virus infection date: 2019-08-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: West Nile Virus (WNV), an emerging and re-emerging RNA virus, is the leading source of arboviral encephalitic morbidity and mortality in the United States. WNV infections are acutely controlled by innate immunity in peripheral tissues outside of the central nervous system (CNS) but WNV can evade the actions of interferon (IFN) to facilitate CNS invasion, causing encephalitis, encephalomyelitis, and death. Recent studies indicate that STimulator of INterferon Gene (STING), canonically known for initiating a type I IFN production and innate immune response to cytosolic DNA, is required for host defense against neurotropic RNA viruses. We evaluated the role of STING in host defense to control WNV infection and pathology in a murine model of infection. When challenged with WNV, STING knock out (-/-) mice displayed increased morbidity and mortality compared to wild type (WT) mice. Virologic analysis and assessment of STING activation revealed that STING signaling was not required for control of WNV in the spleen nor was WNV sufficient to mediate canonical STING activation in vitro. However, STING-/- mice exhibited a clear trend of increased viral load and virus dissemination in the CNS. We found that STING-/- mice exhibited increased and prolonged neurological signs compared to WT mice. Pathological examination revealed increased lesions, mononuclear cellular infiltration and neuronal death in the CNS of STING-/- mice, with sustained pathology after viral clearance. We found that STING was required in bone marrow derived macrophages for early control of WNV replication and innate immune activation. In vivo, STING-/- mice developed an aberrant T cell response in both the spleen and brain during WNV infection that linked with increased and sustained CNS pathology compared to WT mice. Our findings demonstrate that STING plays a critical role in immune programming for the control of neurotropic WNV infection and CNS disease. url: https://www.ncbi.nlm.nih.gov/pubmed/31415679/ doi: 10.1371/journal.ppat.1007899 id: cord-262786-otxpc46a author: Mohammadi, Soheil title: Understanding the Immunologic Characteristics of Neurologic Manifestations of SARS-CoV-2 and Potential Immunological Mechanisms date: 2020-09-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Similar to its predecessors, coronavirus disease 2019 (COVID-19) exhibits neurotrophic properties, which lead to progression of neurologic sequelae. Besides direct viral invasion to the central nervous system (CNS), indirect CNS involvement through viral-mediated immune response is plausible. Aberrant immune pathways such as extreme release of cytokines (cytokine storm), autoimmunity mediated by cross-reactivity between CNS components and viral particles, and microglial activation propagate CNS damage in these patients. Here, we review the currently available evidence to discuss the plausible immunologic pathways that may contribute to the development of COVID-19 neurological complications, namely Alzheimer’s disease, Parkinson’s disease, stroke, multiple sclerosis, Guillain-Barre syndrome, seizure, and brainstem involvement. url: https://www.ncbi.nlm.nih.gov/pubmed/32869183/ doi: 10.1007/s12035-020-02094-y id: cord-275795-ee7qyw5h author: Monette, Anne title: T Lymphocytes as Measurable Targets of Protection and Vaccination Against Viral Disorders date: 2018-10-24 words: 28265.0 sentences: 1205.0 pages: flesch: 38.0 cache: ./cache/cord-275795-ee7qyw5h.txt txt: ./txt/cord-275795-ee7qyw5h.txt summary: We focus on immunity generated against both natural infection and vaccination, where a steady shift in conferred vaccination immunogenicity is observed from quantifying activated and proliferating, long-lived effector memory T cell subsets, as the prominent biomarkers of long-term immunity against viruses and their associated disorders causing high morbidity and mortality rates. Since that time, the occurrence of epidemics and outbreaks are now at lower risk, following the introduction of massive vaccination programs able to induce immune system targeting of viruses causing severe disorders affecting distinct geographical locations, and with many epidemiological reports demonstrating long-term efficacy of viral control of non-naïve populations. This approach is being developed to use virus-infected cell-killing antibodies that produce an antiviral environment; these termed antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, which are predicted to link innate and adaptive immune responses, and is becoming possible due to new technologies for rapid isolation and characterization of monoclonal antibodies targeting conserved regions of influenza virus, reviewed in Jegaskanda et al. abstract: Continuous epidemiological surveillance of existing and emerging viruses and their associated disorders is gaining importance in light of their abilities to cause unpredictable outbreaks as a result of increased travel and vaccination choices by steadily growing and aging populations. Close surveillance of outbreaks and herd immunity are also at the forefront, even in industrialized countries, where previously eradicated viruses are now at risk of re-emergence due to instances of strain recombination, contractions in viral vector geographies, and from their potential use as agents of bioterrorism. There is a great need for the rational design of current and future vaccines targeting viruses, with a strong focus on vaccine targeting of adaptive immune effector memory T cells as the gold standard of immunity conferring long-lived protection against a wide variety of pathogens and malignancies. Here, we review viruses that have historically caused large outbreaks and severe lethal disorders, including respiratory, gastric, skin, hepatic, neurologic, and hemorrhagic fevers. To observe trends in vaccinology against these viral disorders, we describe viral genetic, replication, transmission, and tropism, host-immune evasion strategies, and the epidemiology and health risks of their associated syndromes. We focus on immunity generated against both natural infection and vaccination, where a steady shift in conferred vaccination immunogenicity is observed from quantifying activated and proliferating, long-lived effector memory T cell subsets, as the prominent biomarkers of long-term immunity against viruses and their associated disorders causing high morbidity and mortality rates. url: https://www.sciencedirect.com/science/article/pii/S1937644818300844 doi: 10.1016/bs.ircmb.2018.07.006 id: cord-021069-v9f9874x author: Morrison, Lynda A. title: Viral pathogenesis and central nervous system infection date: 2004-11-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Both host defense and viral genetic factors influence the development of viral infection and disease. Due to the presence of the blood-brain barrier, infection of the central nervous system creates additional complexities in interactions between a virus and its host. Stages in viral pathogenesis defined as (1) virus entry, (2) spread, (3) tropism, (4) virulence and injury to the host, and (5) the outcome of infection are discussed for viral infections in general and those aspects unique to infections of the central nervous system. Information about neuronal physiology and function has also been revealed through studying virus infection. An increased understanding of viral pathogenetic mechanisms and host response to infection raises interesting possibilities for vaccine development and for basic studies in neurology and neurobiology. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148964/ doi: 10.1016/1044-5765(91)90002-6 id: cord-018042-qt7055fw author: Müller, Marcus title: Chemokine Actions in the CNS: Insights from Transgenic Mice date: 2008 words: 5804.0 sentences: 268.0 pages: flesch: 42.0 cache: ./cache/cord-018042-qt7055fw.txt txt: ./txt/cord-018042-qt7055fw.txt summary: So while constitutive, astrocyte-targeted production of CXCL10 can promote the recruitment of leukocytes to the CNS, this chemokine lacks the ability to further influence these cells, in particular, to drive a functional immune response. Although it has been possible to produce stimulus-evoked encephalopathy in MBP-and GFAP-CCL2 transgenic mice by systemic innate immune challenge these disorders are largely transient and therefore do not model the increased levels of CNS CCL2 that have been reported to occur in chronic neurological diseases such as human immunodeficiency virus type 1-associated dementia, amyotrophic lateral sclerosis, and multiple sclerosis. It is speculated that CCL21 derived from transgenic oligodendrocytes in the brain of the MBP-CCL21 mice may have interacted with CXCR3 on microglia inducing an inflammatory response that led to the influx of inflammatory cells into the CNS. Functional expression of the lymphoid chemokines CCL19 (ELC) and CCL 21 (SLC) at the blood-brain barrier suggests their involvement in G-protein-dependent lymphocyte recruitment into the central nervous system during experimental autoimmune encephalomyelitis abstract: Historically the central nervous system (CNS) has been viewed as a relatively immune sheltered tissue. Under physiological conditions the CNS is devoid of leukocytes, including professional antigen presenting cells (APC), is deficient in key immune accessory molecules such as major histocompatibility molecules (MHC) and is protected by an effective blood brain barrier. Significantly, however, in numerous pathological states including infectious diseases and autoimmune disorders (e.g. multiple sclerosis) immune cells are effectively recruited to and infiltrate in the CNS. This immune response can be a two-edged sword required on the one hand to control infection and facilitate tissue repair and regeneration but on the other causing tissue injury that can result in life threatening complications. Therefore, understanding the mechanisms that control the trafficking of leukocytes to the CNS and the subsequent interactions between these cells that contribute to tissue injury has significant implications. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122825/ doi: 10.1007/978-0-387-73894-9_10 id: cord-320909-p93gxjm2 author: Natoli, S. title: Does SARS‐Cov‐2 invade the brain? Translational lessons from animal models date: 2020-05-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The current coronavirus disease (COVID‐19) outbreak, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has raised the possibility of potential neurotropic properties of this virus. Indeed, neurological sequelae of SARS‐CoV‐2 infection have already been reported and highlight the relevance of considering the neurological impact of coronavirus (CoV) from a translational perspective. Animal models of SARS and Middle East respiratory syndrome, caused by structurally similar CoVs during the 2002 and 2012 epidemics, have provided valuable data on nervous system involvement by CoVs and the potential for central nervous system spread of SARS‐CoV‐2. One key finding that may unify these pathogens is that all require angiotensin‐converting enzyme 2 as a cell entry receptor. The CoV spike glycoprotein, by which SARS‐CoV‐2 binds to cell membranes, binds angiotensin‐converting enzyme 2 with a higher affinity compared with SARS‐CoV. The expression of this receptor in neurons and endothelial cells hints that SARS‐CoV‐2 may have higher neuroinvasive potential compared with previous CoVs. However, it remains to be determined how such invasiveness might contribute to respiratory failure or cause direct neurological damage. Both direct and indirect mechanisms may be of relevance. Clinical heterogeneity potentially driven by differential host immune‐mediated responses will require extensive investigation. Development of disease models to anticipate emerging neurological complications and to explore mechanisms of direct or immune‐mediated pathogenicity in the short and medium term is therefore of great importance. In this brief review, we describe the current knowledge from models of previous CoV infections and discuss their potential relevance to COVID‐19. url: https://www.ncbi.nlm.nih.gov/pubmed/32333487/ doi: 10.1111/ene.14277 id: cord-253201-r6vsa0pw author: Nazari, S. title: Central Nervous System Manifestations in COVID-19 Patients: A Systematic Review and Meta-analysis date: 2020-07-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Background: At the end of December 2019, a novel respiratory infection, initially reported in China, known as COVID-19 initially reported in China, and later known as COVID-19, led to a global pandemic. Despite many studies reporting respiratory infections as the primary manifestations of this illness, an increasing number of investigations have focused on the central nervous system (CNS) manifestations in COVID-19. In this study, we aimed to evaluate the CNS presentations in COVID-19 patients in an attempt to identify the common CNS features and provide a better overview to tackle this new pandemic. Methods: In this systematic review and meta-analysis, we searched PubMed, Web of Science, Ovid, Embase, Scopus, and Google Scholar. Included studies were publications that reported the CNS features between January 1st, 2020, to April 20th, 2020. The data of selected studies were screened and extracted independently by four reviewers. Extracted data analyzed by using STATA statistical software. The study protocol registered with PROSPERO (CRD42020184456). Results: Of 2353 retrieved studies, we selected 64 studies with 11282 patients after screening. Most of the studies were conducted in China (58 studies). The most common CNS symptom of COVID-19 were Headache (8.69%, 95%CI: 6.76%-10.82%), Dizziness (5.94%, 95%CI: 3.66%-8.22%), and Impaired consciousness (1.9%, 95%CI: 1%-2.79%). Conclusions: The growing number of studies have reported COVID-19, CNS presentations as remarkable manifestations that happen. Hence, understanding the CNS characteristics of COVID-19 can help us for better diagnosis and ultimately prevention of worse outcomes. url: https://doi.org/10.1101/2020.07.21.20158691 doi: 10.1101/2020.07.21.20158691 id: cord-342204-9tgxijvn author: Nuzzo, Domenico title: Potential neurological effects of severe COVID-19 infection date: 2020-07-03 words: 3227.0 sentences: 183.0 pages: flesch: 44.0 cache: ./cache/cord-342204-9tgxijvn.txt txt: ./txt/cord-342204-9tgxijvn.txt summary: In this axis, virus-induced inflammation and oxidative stress could be the common mechanisms responsible for CoV neurological symptoms. People with COVID-19 generally develop respiratory symptoms but the increasing evidence shows that some patients with a severe infection also develop neurological ailments like confusion, stroke, seizure, or loss of smell and taste. Recent studies discussed the neuroinvasive potential of SARS-CoV-2; in fact, some infected subjects did show neurological effects. In fact, detection of some RNA of human-coronavirus in human brain samples clearly demonstrates that these respiratory pathogens are naturally neuroinvasive in J o u r n a l P r e -p r o o f humans and suggests that they establish a persistent infection in human CNS (Arbour et al., 2000) . Therefore, inflammation and oxidative stress systemic, induced by SARS-CoV-2 lung injury, could has effect in CNS causing neuronal dysfunction. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients abstract: Coronaviruses (CoVs) are large positive stranded enveloped RNA viruses that generally cause enteric and respiratory diseases in humans and in animals. Most human CoVs have recently attracted global attention to their lethal potential and great infectious capacity. A highly pathogenic CoV, called COVID-19 or SARS‐CoV2, dramatically emerged in December 2019 in Wuhan, China. This new CoV has caused severe pneumonia in China and rapidly spreads around the world, the COVID-19 pandemic. Growing evidence pieces show that viruses, such as CoVs, can enter the central nervous system from different pathways and inducing neurotoxicity. Therefore, it is urgent to make clear whether SARS-CoV-2 has access to the central nervous system and can cause direct neuronal effects. Moreover, a brain–lung–brain axis is been proposed from the scientific community where severe neurological dysfunction and injury are associated with lung injury, and vice versa. In this axis, virus-induced inflammation and oxidative stress could be the common mechanisms responsible for CoV neurological symptoms. Therefore, is important to make clear whether SARS-CoV-2 lung damage can cause indirect or indirect neuronal effects. url: https://www.sciencedirect.com/science/article/pii/S0168010220303990?v=s5 doi: 10.1016/j.neures.2020.06.009 id: cord-017144-k7fqneup author: Oleszak, Emilia L. title: Nitric Oxide in TMEV date: 2005 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: We and others have previously investigated the role of inducible nitric oxide synthase (iNOS) on early acute and late chronic demyelinating disease induced by Theiler’s Murine Encephalomyelitis Virus (TMEV). Infection of susceptible SJL mice with this virus serves as an excellent model of virus-induced demyelinating disease, such as multiple sclerosis (MS). iNOS transcripts and protein were detected in brains and spinal cords of TMEV-infected SJL mice during early acute disease, which resembles polioencephalomyelitis. Similar level of expression of iNOS has been found in resistant B6 mice, which develop only early acute disease. Weak iNOS staining was detected in reactive astrocytes and in leptomeningeal infiltrates in TMEV-infected SJL mice at 42 days post infection (p.i.), corresponding to early phase of chronic demyelinating disease, but not at 66 and 180 days p.i. corresponding to advanced and terminal stages of the disease, respectively. Results from other laboratories demonstrated that, blocking of NO by treatment of TMEV-infected SJL mice with amino guanidine (AG), a specific inhibitor of NO resulted in delay of late chronic demyelinating disease. However this protective effect of NO inhibitor depended on the temporal phase of the disease, type of cells expressing iNOS and the time of administration of AG. The results from our laboratory suggests that NO expressed during early acute disease is beneficial to the host through induction of apoptosis of infiltrating T cells and resolution of encephalitis, but its role in myelin/oligodendrocytes damage during late chronic demyelinating disease is not clear and it may depend on availability of superoxide and formation of peroxynitrite. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121632/ doi: 10.1007/0-387-25518-4_35 id: cord-268341-103xf3dw author: Parra, Beatriz title: Kinetics of Cytokine mRNA Expression in the Central Nervous System Following Lethal and Nonlethal Coronavirus-Induced Acute Encephalomyelitis date: 1997-07-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract The potential role(s) of cytokines in the reduction of infectious virus and persistent viral infection in the central nervous system was examined by determining the kinetics of cytokine mRNA expression following infection with the neurotropic JHM strain of mouse hepatitis virus. Mice were infected with an antibody escape variant which produces a nonlethal encephalomyelitis and compared to a clonal virus population which produces a fulminant fatal encephalomyelitis. Infection with both viruses induced the accumulation of mRNAs associated with Th1- and Th2-type cytokines, including IFN-γ, IL-4, and IL-10. Peak mRNA accumulations were coincident with the clearance of virus and there was no obvious differences between lethally and nonlethally infected mice. TNF-α mRNA was induced more rapidly in lethally infected mice compared to mice undergoing a nonfatal encephalomyelitis. Rapid transient increases in the mRNAs encoding IL-12, iNOS, IL-1α, IL-1β, and IL-6 occurred following infection. Nonlethal infections were associated with increased IL-12, IL-1β, and earlier expression of IL-6, while lethal infections were associated with increased iNOS and IL-1α mRNA. These data suggest a rapid but differential response within the central nervous system cells to infection by different JHMV variants. However, neither the accumulation nor kinetics of induction provide evidence to distinguish lethal infections from nonlethal infections leading to a persistent infection. Accumulation of both Th1 and Th2 cytokines in the central nervous system of JHMV-infected mice is consistent with the participation of both cytokines and cell immune effectors during resolution of acute viral-induced encephalomyelitis. url: https://api.elsevier.com/content/article/pii/S004268229798613X doi: 10.1006/viro.1997.8613 id: cord-311847-2czqs84q author: Pennisi, Manuela title: SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms date: 2020-07-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction. url: https://www.ncbi.nlm.nih.gov/pubmed/32751841/ doi: 10.3390/ijms21155475 id: cord-008523-avkgldnp author: Perlman, Stanley title: Selection of and evasion from cytotoxic T cell responses in the central nervous system date: 2004-01-07 words: 8866.0 sentences: 401.0 pages: flesch: 44.0 cache: ./cache/cord-008523-avkgldnp.txt txt: ./txt/cord-008523-avkgldnp.txt summary: In mice that were transgenic for a T cell receptor (TCR) specific for lymphocytic choriomeningitis virus (LCMV), infection with LCMV resulted in the rapid appearance of virus mutated in the target CTL epitope. In these mice, CTLs recognizing multiple epitopes are detected, suggesting that an immune response directed against several epitopes precluded the selection of CTL escape mutants, at least in settings in which virus clearance was relatively efficient. One of the best examples of a pathological setting in which CTL escape mutants contribute to virus persistence and the development of disease is that of mice infected with the neurotropic coronavirus, mouse hepatitis virus--strain JHM (MHV-JHM). These results suggest that CTL escape mutants are critical in virus persistence and in the development of clinical disease in mice infected with MHV-JHM. The selection of CTL escape mutants in the CNS of MHV-infected mice demonstrates that MHV infection of a cell expressing MHC class I antigen is a critical part of the pathogenic process. abstract: Cytotoxic CD8 T lymphocytes (CTLs) are critical for the clearance of noncytopathic viruses from infected cells. This chapter discusses one mechanism used by viruses to persist—namely, the selection of a variant virus in which changes in the sequence of a CTL epitope abrogate recognition. The unique features of cytotoxic CD8 T cell function in the central nervous system (CNS) are discussed. The role of CTL escape mutants in the viral evasion of the immune system and subsequent disease progression in non-CNS infections are summarized. The immune response in the CNS is similar to the response in extraneural tissue, but several aspects of the activation of the immune response, cellular trafficking, and antigen presentation are unique to the CNS. Although the CNS has classically been considered a site of immune privilege, surveillance of the normal CNS by circulating, activated lymphocytes occurs, with a limited number of lymphocytes being present in the normal CNS at any given time. In mice infected with mouse hepatitis virus and in some humans persistently infected with human immunodeficiency virus type1, hepatitis B virus or hepatitis C virus, CTL escape mutants play an important role in virus amplification and disease progression. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131566/ doi: 10.1016/s0065-3527(01)56029-7 id: cord-338235-vz2d2x18 author: Pinschewer, Daniel D. title: T cells can mediate viral clearance from ependyma but not from brain parenchyma in a major histocompatibility class I- and perforin-independent manner date: 2010-03-30 words: 7277.0 sentences: 349.0 pages: flesch: 45.0 cache: ./cache/cord-338235-vz2d2x18.txt txt: ./txt/cord-338235-vz2d2x18.txt summary: This indicated that it was indeed the absence of perforin-dependent cytolytic pathways rather than a general impairment of CD8 + T cell Virus clearance from ependyma To gain further insights on how rLCMV/INDG persisted in the CNS of perforin-deficient, TCRb À/À and RAG À/À mice but not in C57BL/6 controls, we performed histological time course analyses of viral antigen and of infiltrating CD8 + T cells. However, C57BL/6 wild-type animals eliminated the virus by Day 8, whereas slowly but steadily increasing numbers of infected cells were found within the CNS parenchyma of perforin-deficient, TCRb À/À and RAG À/À mice on Days 8, 10 Frequencies of NP396-specific CD8 + T cells in blood were determined on Day 8 using MHC class I tetramers. Total viral RNA loads in the brain of perforin-deficient, MHCI À/À , TCRb À/À and RAG À/À mice are similar as determined by quantitative RT-PCR (Fig. 6C) , providing evidence that within the brain parenchyma, adaptive immune pathways other than MHCI-and perforin-dependent T cell clearance do not substantially influence rLCMV/INDG persistence. abstract: Viral infection of the central nervous system can lead to disability and death. Yet the majority of viral infections with central nervous system involvement resolve with only mild clinical manifestations, if any. This is generally attributed to efficient elimination of the infection from the brain coverings, i.e. the meninges, ependyma and chorioplexus, which are the primary targets of haematogeneous viral spread. How the immune system is able to purge these structures from viral infection with only minimal detrimental effects is still poorly understood. In the present work we studied how an attenuated lymphocytic choriomeningitis virus can be cleared from the central nervous system in the absence of overt disease. We show that elimination of the virus from brain ependyma, but not from brain parenchyma, could be achieved by a T cell-dependent mechanism operating independently of major histocompatibility class I antigens and perforin. Considering that cytotoxic T lymphocyte-mediated cytotoxicity is a leading cause of viral immunopathology and tissue damage, our findings may explain why the most common viral intruders of the central nervous system rarely represent a serious threat to our health. url: https://doi.org/10.1093/brain/awq028 doi: 10.1093/brain/awq028 id: cord-022594-fx044gcd author: Pirko, Istvan title: Demyelinating Disorders of the Central Nervous System date: 2009-05-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158368/ doi: 10.1016/b978-141603618-0.10048-7 id: cord-005393-rhji4io9 author: Popko, Brian title: The effects of interferon-γ on the central nervous system date: 1997 words: 7969.0 sentences: 418.0 pages: flesch: 42.0 cache: ./cache/cord-005393-rhji4io9.txt txt: ./txt/cord-005393-rhji4io9.txt summary: A large portion of this article is devoted to the substantial circumstantial and experimental evidence that suggests that IFN-γ plays an important role in the pathogenesis of the demyelinating disorder multiple sclerosis (MS) and its animal model experimental allergic encephalomyelitis (EAE). For example, the genes encoding the gaunylate binding protein and the IgG Fc receptor are induced in this way: Other genes that are stimulated by IFN-~/, such as the class I and class II molecules of the major histocompatibility complex (MHC), require a longer period (several hours) before transcriptional induction is detected. Many of the pathological events Observed in MS and EAE, such as increased MHC expression, macrophage activation, increased expression of leukocyte adhesion molecules on blood-brain barrier endothelial cells (Olsson, 1992) , and reactive gliosis (Balasingam et al., 1994) , are consistent with the known effects of IFN-~,. (1984) demonstrated a dramatic increase in the expression of the MHC class I glycoprotein in astrocytes, neurons, oligodendrocytes and microglia following the delivery of IFN-y to the CNS of 2-dold mice. abstract: Interferon-gamma (IFN-γ) is a pleotropic cytokine released by T-lymphocytes and natural killer cells. Normally, these cells do not traverse the blood-brain barrier at appreciable levels and, as such, IFN-γ is generally undetectable within the central nervous system (CNS). Nevertheless, in response to CNS infections, as well as during certain disorders in which the CNS is affected, T-cell traffic across the blood-brain barrier increases considerably, thereby exposing neuronal and glial cells to the potent effects of IFN-γ. A large portion of this article is devoted to the substantial circumstantial and experimental evidence that suggests that IFN-γ plays an important role in the pathogenesis of the demyelinating disorder multiple sclerosis (MS) and its animal model experimental allergic encephalomyelitis (EAE). Moreover, the biochemical and physiological effects of IFN-γ are discussed in the context of the potential consequences of such activities on the developing and mature nervous systems. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091409/ doi: 10.1007/bf02740619 id: cord-007603-27m9wz0i author: Rall, Glenn F. title: A transgenic mouse model to assess the interaction of cytotoxic T lymphocytes with virally infected, class I MHC-expressing astrocytes date: 2002-11-11 words: 3682.0 sentences: 202.0 pages: flesch: 52.0 cache: ./cache/cord-007603-27m9wz0i.txt txt: ./txt/cord-007603-27m9wz0i.txt summary: Functional antigen-presenting capacity was conferred by the D(b) transgene, as virus-infected primary astrocytes obtained from transgenic BALB/c mice (K(d)I(d)D(d)L(d)) expressing the D(b) molecule were lysed by D(b)-restricted anti-viral CTL. The central nervous system (CNS) has been considered an immune privileged site compared with other organs by virtue of the blood-brain barrier that restricts access of macromolecules and non-activated lymphoid cells from the periphery into the CNS parenchyma and because resident CNS cells such as neurons, oligodendrocytes and astrocytes express negligible to undetectable levels of class I major histocompatibility (MHC) molecules (reviewed in Lampson, 1987) . To establish transgenic mice with astroglial expression of an MHC class I molecule, a minigene encoding the MHC class I antigen D b was placed under the regulatory influence of a modified murine glial fibrillary acidic protein (GFAP) gene (Fig. 1) . abstract: Astrocytes provide crucial support for neurons and their impairment by viruses or their interactions with anti-viral or autoimmune responses could contribute to neurological disease. We have developed a transgenic mouse model to assess lymphocyte-astrocyte interactions. The major histocompatibility complex (MHC) class I molecule, D(b), was expressed in astrocytes under the transcriptional control of regulatory sequences from the glial fibrillary acidic protein (GFAP) gene. Baseline cerebral MHC class I mRNA levels from transgenic mice were elevated over those of non-transgenic controls, and a prominent increase in cerebral MHC class I expression occurred following focal, injury-induced astroglial activation within transgenic brains but not in non-transgenic controls. FACS analysis of explant astrocyte cultures from established transgenic lines demonstrated astroglial expression of the GFAP-D(b) fusion gene at the protein level. Functional antigen-presenting capacity was conferred by the D(b) transgene, as virus-infected primary astrocytes obtained from transgenic BALB/c mice (K(d)I(d)D(d)L(d)) expressing the D(b) molecule were lysed by D(b)-restricted anti-viral CTL. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119529/ doi: 10.1016/0165-5728(94)90163-5 id: cord-007170-svsfu7fj author: Richt, J. A. title: Infection with Borna Disease Virus: Molecular and Immunobiological Characterization of the Agent date: 1992-06-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Borna disease virus (BDV), which seems to be distinct from all other known viruses, exhibits a unique mechanism of pathogenesis. This review highlights several aspects of the biology of infection with this virus and summarizes the preliminary characterization of the agent. Studies on BDV may help to illuminate several important areas of neurobiology, including the mechanisms regulating the replication of a new type of RNA virus in the nuclei of neural cells, the neuroinvasiveness and neurotropism of such viruses, their T cell-mediated immunopathology, tolerance in newborn animals to persistent viral infection of the central nervous system, and behavioral diseases and eating disorders induced by such agents. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109702/ doi: 10.1093/clinids/14.6.1240 id: cord-005146-o3roa7br author: Sasaki, Makoto title: Demyelination and remyelination in the dorsal funiculus of the rat spinal cord after heat injury date: 1989 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Part of the dorsal funiculus of the adult male rat (Wistar) spinal cord was treated for l h at the thoracolumbar level by running hot water, at approximately 48–50 ° C, through a polyethylene tube 2 mm in diameter in contact with the dura. Animals were fixed 1 day to 4 weeks later and the spinal cords were examined by light and electron microscopy. The affected area in the dorsal funiculus was approximately 1 mm long and less than 1 mm wide at the dorsal surface, and varied from 0.4 to 0.7 mm in depth. Within 3 days after treatment, almost all the myelin sheaths in the affected area were degraded, leaving the axons denuded, and at the same time astrocyte endfeet at the glial limiting membrane were swollen and partly destroyed. Almost all the denuded axons remained intact, exhibiting no noticeable morphological changes. There was evidence of a moderate vasogenic oedema, but minimal signs of haemorrhage in the lesion. Seven days after treatment, many immature Schwann cells but no oligodendrocytes were found between the denuded axons. By 2 weeks many of the denuded axons were remyelinated, and by 4 weeks almost all of those axons located near the pial and perivascular surfaces had been remyelinated by Schwann cells, while most of those located in the deep and marginal zones bordering the adjoining intact areas were remyelinated by oligodendrocytes. Longitudinal sections revealed that at nodes of Ranvier PNS-type myelin sheaths were apposed by either intact or newly formed CNS-type myelin sheaths. A typical glial limiting membrane was not reformed beneath the pial surface, but an inconspicuous one was found between the PNS- and CNS-type fibre areas. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088616/ doi: 10.1007/bf01206664 id: cord-267166-ecmayzr6 author: Savarin, Carine title: Distinct Gene Profiles of Bone Marrow-Derived Macrophages and Microglia During Neurotropic Coronavirus-Induced Demyelination date: 2018-06-11 words: 7736.0 sentences: 371.0 pages: flesch: 39.0 cache: ./cache/cord-267166-ecmayzr6.txt txt: ./txt/cord-267166-ecmayzr6.txt summary: While gene expression in CNS infiltrating BMDM was upregulated early following infection and subsequently sustained, microglia expressed a more dynamic gene profile with extensive mRNA upregulation coinciding with peak demyelination after viral control. This study takes advantage of the distinct tissue environments established during EAE and JHMV infection to characterize temporal alterations in gene expression profiles of BMDM versus microglia in a Th1 biased demyelination model. We next evaluated effector functions of BMDM versus microglia associated with JHMV-induced demyelination by comparing gene expression profiles using nCounter analysis of mRNA isolated from purified BMDM and microglia of infected CX3CR1 GFP/+ CCR2 RFP/+ mice. Using a similar approach with Nanostring analysis as in EAE, the present study used gene expression profiling to characterize both BMDM and microglia myeloid functions at various times post JHMV infection. abstract: Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination and axonal loss. Demyelinating lesions are associated with infiltrating T lymphocytes, bone marrow-derived macrophages (BMDM), and activated resident microglia. Tissue damage is thought to be mediated by T cell produced cytokines and chemokines, which activate microglia and/or BMDM to both strip myelin and produce toxic factors, ultimately damaging axons and promoting disability. However, the relative contributions of BMDM and microglia to demyelinating pathology are unclear, as their identification in MS tissue is difficult due to similar morphology and indistinguishable surface markers when activated. The CD4 T cell-induced autoimmune murine model of MS, experimental autoimmune encephalitis (EAE), in which BMDM are essential for demyelination, has revealed pathogenic and repair-promoting phenotypes associated with BMDM and microglia, respectively. Using a murine model of demyelination induced by a gliatropic coronavirus, in which BMDM are redundant for demyelination, we herein characterize gene expression profiles of BMDM versus microglia associated with demyelination. While gene expression in CNS infiltrating BMDM was upregulated early following infection and subsequently sustained, microglia expressed a more dynamic gene profile with extensive mRNA upregulation coinciding with peak demyelination after viral control. This delayed microglia response comprised a highly pro-inflammatory and phagocytic profile. Furthermore, while BMDM exhibited a mixed phenotype of M1 and M2 markers, microglia repressed the vast majority of M2-markers. Overall, these data support a pro-inflammatory and pathogenic role of microglia temporally remote from viral control, whereas BMDM retained their gene expression profile independent of the changing environment. As demyelination is caused by multifactorial insults, our results highlight the plasticity of microglia in responding to distinct inflammatory settings, which may be relevant for MS pathogenesis. url: https://www.ncbi.nlm.nih.gov/pubmed/29942315/ doi: 10.3389/fimmu.2018.01325 id: cord-297325-fbilhauu author: Savarin, Carine title: Self-reactive CD4(+) T cells activated during viral-induced demyelination do not prevent clinical recovery date: 2015-11-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Microbial infections have been implicated in initiating and enhancing severity of autoimmune diseases including the demyelinating disease multiple sclerosis (MS). Nevertheless, the incidence of both acute and persisting viral infections without evidence of autoimmune sequelae suggests that this process is well controlled. The conditions promoting or stemming self-reactive (SR) T cells following viral-induced tissue damage thus need to be better defined. Using a non-fatal viral mouse model of encephalomyelitis associated with demyelination and disability, yet ultimate clinical improvement, this study set out to monitor uptake and presentation of endogenous myelin antigens, as well as induction and fate of SR T cells. METHODS: Activation and central nervous system (CNS) recruitment of myelin-specific CD4 T cells was analyzed by flow cytometry during encephalomyelitis induced by a glia tropic murine coronavirus. Potential antigen-presenting cells (APC) ingesting myelin were characterized by flow cytometry and their ability to activate SR T cells tested by co-culture with carboxyfluorescein succinimidyl ester (CFSE)-labeled myelin-specific CD4 T cells. Endogenous SR T cell kinetics was analyzed within both cervical lymph nodes and CNS by Enzyme-Linked ImmunoSpot (ELISPOT) following viral infection. RESULTS: The data demonstrate the presence of APC capable of activating SR T cells in both draining lymph nodes and the CNS temporally correlating with overt demyelination. While both the CNS-infiltrating myeloid population and microglia ingested myelin, only CNS-infiltrating APC were capable of presenting endogenous myelin antigen to SR T cells ex vivo. Finally, SR T cell activation from the endogenous T cell repertoire was most notable when infectious virus was controlled and paralleled myelin damage. Although SR T cell accumulation peaked in the persistently infected CNS during maximal demyelination, they were not preferentially retained. Their gradual decline, despite ongoing demyelination, suggested minimal re-stimulation and pathogenic function in vivo consistent with the lack of autoimmune symptoms. CONCLUSIONS: The results demonstrate the potential for CNS tissue destruction to induce and recruit SR T cells to the injury site and support a host suppressive mechanism limiting development of autoimmunity. url: https://www.ncbi.nlm.nih.gov/pubmed/26559484/ doi: 10.1186/s12974-015-0426-1 id: cord-022395-rk31pwoa author: Schuller-Levis, Georgia title: Central Nervous System: Viral Infection and Immune-Mediated Inflammation date: 2012-12-02 words: 8843.0 sentences: 471.0 pages: flesch: 41.0 cache: ./cache/cord-022395-rk31pwoa.txt txt: ./txt/cord-022395-rk31pwoa.txt summary: Acute and chronic relapsing EAE can be induced in laboratory animals by an injection of CNS tissue, CNS myelin, myelin basic protein, or more recently, T-cell lines specific for nervous system antigens. Infection with mouse hepatitis virus (MHV), has been shown to block expression of MHC molecules on murine cerebral endothelial cells (see later discussion) (Joseph et al., 1991) . Until recently, the HLA Class I molecules were thought to be the primary, if not the only, HLA recognition structure for CTLs. Studies of measles and Epstein-Barr virus (EBV) infection suggest that HLA Class II molecules can also serve as recognition sites, further expanding the potential action of CTLs. Viral antigens recognized by CTLs have also been expanded beyond the traditional cell surface molecules (Braciale and Braciale, 1986) . The subsequent activation of specific cellular transcription factors in response to extracellular stimuli can induce the expression of virus and lead to CNS disease. Immune response gene products (la antigens) on glial and endothelial cells in virus-induced demyelination abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155647/ doi: 10.1016/b978-0-12-628930-5.50019-9 id: cord-299949-kmn53e2z author: Schultz, Kimberly L.W. title: Immune Responses to Viruses in the CNS date: 2016-05-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: For recovery from infection, the immune response in the central nervous system (CNS) must eliminate or control virus replication without destroying nonrenewable, essential cells. Thus, upon intracellular virus detection, the infected cell must initiate clearance pathways without triggering neuronal cell death. As a result, the inflammatory response must be tightly regulated and unique mechanisms contribute to the immune response in the CNS. Early restriction of virus replication is accomplished by the innate immune response upon activation of pattern recognition receptors in resident cells. Infiltrating immune cells enter from the periphery to clear virus. Antibodies and interferon-γ are primary contributors to noncytolytic clearance of virus in the CNS. Lymphocytes are retained in the CNS after the acute phase of infection presumably to block reactivation of virus replication. url: https://api.elsevier.com/content/article/pii/B9780123742797140226 doi: 10.1016/b978-0-12-374279-7.14022-6 id: cord-285493-eg2ltip6 author: Schwab, S. title: Non-suppurative Meningoencephalitis of Unknown Origin in Cats and Dogs: an Immunohistochemical Study date: 2007-02-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Non-suppurative meningoencephalitis of unknown cause is a frequent finding in dogs and cats. Fifty-three dogs and 33 cats with non-suppurative meningoencephalitis of unknown aetiology were examined immunohistochemically for 18 different infectious agents, including viruses, bacteria and prion protein(Sc). In 14 (26%) of the dogs and 13 (39%) of the cats a causative agent was identified in the central nervous system (CNS), two dogs and one cat giving positive results for two infectious agents simultaneously. The study revealed infections with known causative agents (porcine herpes virus 1, feline infectious peritonitis virus, Escherichia coli) and a new disease pattern of parvovirus infection in the CNS of dogs and cats. Infection of the CNS with feline leukaemia virus was found in a cat. Five dogs and four cats gave positive results for West Nile virus (WNV) antigen. In one dog, canine parainfluenza virus antigen was detected in the brain. Four dogs and four cats gave positive results for encephalomyocarditis virus (EMCV). The significance of the detection of WNV and EMCV antigen requires further study. The aetiology remained undetermined in 39 dogs (74%) and 20 cats (61%). Although it is possible that non-infectious causes play a more important role than previously thought, infections with hitherto unrecognized agents cannot be ruled out. url: https://www.ncbi.nlm.nih.gov/pubmed/17275833/ doi: 10.1016/j.jcpa.2006.11.006 id: cord-322728-10m3xscs author: Severance, Emily G. title: Chapter 29 Role of Immune and Autoimmune Dysfunction in Schizophrenia date: 2016-12-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract In this chapter, we review data in support of the concept that immune system dysregulation is the most plausible explanation that reconciles gene by environmental interactions in schizophrenia. Early investigations of this topic demonstrated aspects of aberrant activation of humoral immunity, including autoimmunity, associated with schizophrenia, whereas current research efforts have expanded this theme to include elements of innate immunity. Advances in our understanding of inflammation and molecules of both the adaptive and innate immune system and their functional roles in standard brain physiology provide an important context by which schizophrenia might arise as the result of the coupling of immune and neurodevelopmental dysregulation. url: https://www.sciencedirect.com/science/article/pii/B9780128009819000298 doi: 10.1016/b978-0-12-800981-9.00029-8 id: cord-355413-ls2nud43 author: Shi, Fu-Dong title: Nature killer cells in the central nervous system date: 2010-01-29 words: 6858.0 sentences: 345.0 pages: flesch: 45.0 cache: ./cache/cord-355413-ls2nud43.txt txt: ./txt/cord-355413-ls2nud43.txt summary: The pathogenic mechanism observed appeared to represent a novel type of autoimmune reaction: an exogenously/chemically induced alteration in a specific subset of cells that was suggested to target them for direct NK cell-mediated killing. The migration of NK cells to the CNS during inflammatory responses and lack of inhibitory signal MHC class I expression within the CNS invites prediction that direct cytolytic effects of NK cells contribute to oligodendrocyte damage and demyelination to CNS diseases such as MS. Intracerebral infection of RAG1 / mice with a recombinant CXCL10-expressing murine coronavirus (MHV) resulted in protection from disease and increased survival that correlated with a significant increase in recruitment and activation of NK cells within the CNS (Walsh et al., 2007) . Associated with decreased resistance to viral infection, CCR5 / mice yielded significantly more virus and expressed higher levels of tumour necrosis factor alpha (TNF-), CXCL1, CCL2, CCL3 and CCL5 in the vagina, spinal cord, and/or brain stem than did wild-type mice. abstract: Natural killer (NK) cells, a prominent component of the innate immune system, are large granular lymphocytes that respond rapidly to a variety of insults via cytokine secretion and cytolytic activity. Recently, there has been growing insight into the biological functions of NK cells, in particular into their roles in infection, tumorurveillance and autoimmunity. Under these pathophysiological circumstances, NK cells readily home to the central nervous system (CNS) tissues to combat infection and presumably to curb progression of tumor. Bystander neuronal and/or glial cell damage can occur in this setting. Paradoxically, NK cells appear to have an inhibitory role for autoimmune responses within the CNS. As in the periphery, NK cells act in concert with T cells and other lymphocytes responsible for CNS pathology and immune regulation. Insights into the molecular signals and pathways governing the diverse biological effects of NK cells are keys for designing NK cell-based therapy for CNS infections, tumor and autoimmune diseases.NK cells readily accumulate in homing to CNS tissues under the pathophysiological situations. This process is tightly controlled by a number of chemokines and chemokine receptors. There is ample of evidence that NK cells within the CNS contribute to the control of infections and might limit progression of certain tumor. Bystander neuronal and/or glial cell damage can occur. In certain autoimmune conditions of the CNS, NK cells appear to have an inhibitory role. Disassociation of disease-inhibiting versus disease-promoting effects of NK cells is a key to harnessing NK cells for therapeutic purposes. To achieve this goal, a generation of genetic models with selective NK cell deficiency, and development of reagents (antibodies) for visualizing subsets of NK cells in situ will be necessary. url: https://www.sciencedirect.com/science/article/pii/B9780123704542000284 doi: 10.1016/b978-0-12-370454-2.00028-4 id: cord-271011-5stsx5je author: Singh, M. title: Inflammatory cerebrospinal fluid analysis in cats: clinical diagnosis and outcome date: 2005-03-09 words: 6930.0 sentences: 400.0 pages: flesch: 53.0 cache: ./cache/cord-271011-5stsx5je.txt txt: ./txt/cord-271011-5stsx5je.txt summary: The purpose of this study was to determine if signalment, clinical signs, CSF analysis, additional clinicopathological data and diagnostic imaging could be used to determine the specific aetiology of the CNS disease in cats with inflammatory CSF. Based on the results, clinical information, clinical pathology and ancillary testing procedures the following classifications of disease could be made: 1, feline infectious peritonitis (FIP); 2, Cryptococcus species infection; 3, Toxoplasma species infection; 4, other meningoencephalitis; 5, thiamine deficiency; 6, lymphoma; 7, other neoplasia; 8, trauma; 9, intervertebral disc disease; 10, spinal cord granuloma and 11, undiagnosed (Table 2) . A presumptive diagnosis of FIP was made based on age, a suppurative or mixed inflammatory CSF, poor response to treatment, elevated serum or body cavity effusion FeCoV antibody titre or a reduced albumin:globulin ratio (!0.5) of serum or body cavity effusions. A presumptive diagnosis was made based on a mild suppurative-mixed CSF inflammation, normal-mildly increased CSF protein levels and positive IgG antibody titre. abstract: The medical records of 62 cats with clinical signs of central nervous system disease and accompanying inflammatory cerebrospinal fluid (CSF) analysis were examined retrospectively to determine if signalment, clinical signs, CSF analysis and ancillary testing could accurately predict the type of central nervous system disease that was present. An inflammatory CSF was defined as one in which a total nucleated cell count was greater than 5 cells/μl or one in which the total nucleated cell count was normal but the nucleated cell differential count was abnormal. Sex, degree of CSF inflammation, neuroanatomical location and systemic signs provided little contributory information to the final diagnosis. In 63% of the cases a presumptive diagnosis could be made based on a combination of clinical signs, clinicopathological data and ancillary diagnostic tests. CSF analysis alone was useful only in the diagnosis of cats with feline infectious peritonitis, Cryptococcus species infection, lymphoma and trauma. Overall, despite extensive diagnostic evaluation, a specific diagnosis could not be made in 37% of cats. The prognosis for cats with inflammatory CSF was poor with 77% of cats surviving less than 1 year. url: https://www.ncbi.nlm.nih.gov/pubmed/15771944/ doi: 10.1016/j.jfms.2004.07.001 id: cord-003199-03c9rx3o author: Singh, Manmeet title: Intracranial Inoculation Is More Potent Than Intranasal Inoculation for Inducing Optic Neuritis in the Mouse Hepatitis Virus-Induced Model of Multiple Sclerosis date: 2018-09-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Neurotropic strains of mouse hepatitis virus (MHV) induce acute inflammation and chronic demyelination in the spinal cord and optic nerves mediated by axonal spread following intracranial inoculation in mice, with pathologic features similar to the human demyelinating disease multiple sclerosis. Spinal cord demyelination is also induced following intranasal inoculation with neurotropic MHV strains, however much higher viral doses are required as compared to intracranial inoculation. Recently, it was shown that intranasal administration of low concentrations of proteins leads to significant, rapid accumulation of protein in the optic nerve and in the eye, with only low levels reaching spinal cord and other brain regions. Thus, we examined whether intranasal inoculation with MHV at doses equivalent to those given intracranially could induce optic neuritis—inflammation, demyelination and loss of retinal ganglion cells (RGCs) in the optic nerve with or without inducing spinal cord demyelination. Four week old male C57BL/6J mice were inoculated intracranially with the recombinant demyelinating strain RSA59, or intranasally with RSA59 or the non-demyelinating strain RSMHV2 as control. One month post-inoculation, mice inoculated intracranially with RSA59 had significant myelin loss in both spinal cord and optic nerves, with significant loss of RGCs as well, consistent with prior studies. As expected, intranasal inoculation with RSA59 failed to induce demyelination in spinal cord; however, it also did not induce optic nerve demyelination. No acute inflammation was found, and no viral antigen was detected, in the optic nerve or retina 1 day after inoculation. Results confirm the neurotropic effects of RSA59 following intracranial inoculation, and suggest that direct infection with axonal transport of virus from brain to spinal cord and optic nerve is required to induce demyelinating disease. These studies suggest that MHV does not selectively concentrate in optic nerve and retina to sufficient levels to induce demyelination following intranasal inoculation. Intracranial inoculation should continue to be considered a preferred method for studies of MHV-induced optic neuritis and central nervous system (CNS) demyelinating disease. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132074/ doi: 10.3389/fcimb.2018.00311 id: cord-303741-1ou0cy5k author: Stafstrom, Carl E. title: COVID-19: Neurological Considerations in Neonates and Children date: 2020-09-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The ongoing worldwide pandemic of the novel human coronavirus SARS-CoV-2 and the ensuing disease, COVID-19, has presented enormous and unprecedented challenges for all medical specialists. However, to date, children, especially neonates, have been relatively spared from the devastating consequences of this infection. Neurologic involvement is being increasingly recognized among adults with COVID-19, who can develop sensory deficits in smell and taste, delirium, encephalopathy, headaches, strokes, and peripheral nervous system disorders. Among neonates and children, COVID-19-associated neurological manifestations have been relatively rare, yet reports involving neurologic dysfunction in this age range are increasing. As discussed in this review, pediatric neurologists and other pediatric specialists should be alert to potential neurological involvement by this virus, which might have neuroinvasive capability and carry long-term neuropsychiatric and medical consequences. url: https://www.ncbi.nlm.nih.gov/pubmed/32927628/ doi: 10.3390/children7090133 id: cord-283850-kt8n6pg2 author: Steardo, Luca title: Psychiatric face of COVID-19 date: 2020-07-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The Coronavirus Disease 2019 (COVID-19) represents a severe multiorgan pathology which, besides cardio-respiratory manifestations, affects the function of the central nervous system (CNS). The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similarly to other coronaviruses demonstrate neurotropism; the viral infection of the brain stem may complicate the course of the disease through damaging central cardio-respiratory control. The systemic inflammation as well as neuroinflammatory changes are associated with massive increase of the brain pro-inflammatory molecules, neuroglial reactivity, altered neurochemical landscape and pathological remodelling of neuronal networks. These organic changes, emerging in concert with environmental stress caused by experiences of intensive therapy wards, pandemic fears and social restrictions, promote neuropsychiatric pathologies including major depressive disorder, bipolar disorder (BD), various psychoses, obsessive-compulsive disorder and post-traumatic stress disorder. The neuropsychiatric sequelae of COVID-19 represent serious clinical challenge that has to be considered for future complex therapies. url: https://doi.org/10.1038/s41398-020-00949-5 doi: 10.1038/s41398-020-00949-5 id: cord-345339-kyboibtq author: Steiner, Israel title: Infection and the etiology and pathogenesis of multiple sclerosis date: 2001 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Multiple sclerosis (MS) currently defies clinical and scientific definitions, and carries a prognosis that remains practically unchanged despite many years of intensive research. Although the prevailing dogma is that MS is an immune-mediated condition, it fulfills none of the criteria of an autoimmune disease. On the other hand, there is enough significant data to suggest that infectious agents(s) could be involved in either direct damage to the white matter or induce inflammatory responses that secondarily affect the brain. Our goal here is to review the data supporting the possibility that infection has a critical role in the disease, examine the list of potential candidates that have been suggested, and outline an approach regarding the potential role of infectious agents in the etiology and pathogenesis of MS. url: https://www.ncbi.nlm.nih.gov/pubmed/11898529/ doi: 10.1007/s11910-001-0030-x id: cord-270084-xs0pbcip author: Stohlman, Stephen A. title: Delayed-type hypersensitivity response in the central nervous system during JHM virus infection requires viral specificity for protection date: 1988-09-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract The JHM strain of mouse hepatitis virus (JHMV) elicits an I-A-restricted delayed-type hypersensitivity (DTH) response mediated by a Thy-1+, Lyt-1+, and CD4+ T cell. Adoptive transfer of these polyclonal CD4+ T cells from immunized mice prevents death in lethally infected recipients without significantly reducing virus titer in the central nervous system (CNS). These observations raise the possibility that the recruitment of mononuclear cells into the CNS may play a critical role in survival from a lethal CNS infection. Transient DTH response to nonviral antigens induced an accumulation of monocytes in the CNS that was maximal at 48 h post-challenge and virtually resolved by 5 days post-challenge. By contrast the induction of prolonged DTH responses resulted in the accumulation of a large number monocytes that persisted in the CNS for at least 5 days post-challenge. Neither type of DTH reaction suppressed virus replication or prevented death from concomitant lethal JHMV infection. url: https://www.ncbi.nlm.nih.gov/pubmed/2842378/ doi: 10.1016/0165-5728(88)90007-0 id: cord-351398-ftkrd1tj author: Stohlman, Stephen A. title: Viral Induced Demyelination date: 2006-04-05 words: 8223.0 sentences: 374.0 pages: flesch: 36.0 cache: ./cache/cord-351398-ftkrd1tj.txt txt: ./txt/cord-351398-ftkrd1tj.txt summary: This suggests that demyelination induced by viral infections can result from: 1) a direct viral infection of oligodendroglia resulting in cell death with degeneration of myelin and its subsequent removal; 2) a persistent viral infection, in the presence or absence of infectious virus, resulting in the loss of normal cellular homeostasis and subsequent oligodendroglial death; 3) a vigorous virus‐specific inflammatory response wherein the virus replicates in a cell type other than oligodendroglia, but cytokines and other immune mediators directly damage the oligodendroglia or the myelin sheath; or 4) infection initiates activation of an immune response specific for either oligodendroglia or myelin components. Although the relevance of these neuroantigen specific T cells to the progression of chronic demyelination is still not clear, the data clearly demonstrate activation of immunity to host antigens during inflammation induced by a persistent viral infection. abstract: Viral induced demyelination, in both humans and rodent models, has provided unique insights into the cell biology of oligodendroglia, their complex cell‐cell interactions and mechanisms of myelin destruction. They illustrate mechanisms of viral persistence, including latent infections in which no infectious virus is readily evident, virus reactivation and viral‐induced tissue damage. These studies have also provided excellent paradigms to study the interactions between the immune system and the central nervous system (CNS). Although of interest in their own right, an understanding of the diverse mechanisms used by viruses to induce demyelination may shed light into the etiology and pathogenesis of the common demyelinating disorder multiple sclerosis (MS). This notion is supported by the persistent view that a viral infection acquired during adolescence might initiate MS after a long period of quiescence. Demyelination in both humans and rodents can be initiated by infection with a diverse group of enveloped and non‐enveloped RNA and DNA viruses (Table 1). The mechanisms that ultimately result in the loss of CNS myelin appear to be equally diverse as the etiological agents capable of causing diseases which result in demyelination. Although demyelination can be a secondary result of axonal loss, in many examples of viral induced demyelination, myelin loss is primary and associated with axonal sparing. This suggests that demyelination induced by viral infections can result from: 1) a direct viral infection of oligodendroglia resulting in cell death with degeneration of myelin and its subsequent removal; 2) a persistent viral infection, in the presence or absence of infectious virus, resulting in the loss of normal cellular homeostasis and subsequent oligodendroglial death; 3) a vigorous virus‐specific inflammatory response wherein the virus replicates in a cell type other than oligodendroglia, but cytokines and other immune mediators directly damage the oligodendroglia or the myelin sheath; or 4) infection initiates activation of an immune response specific for either oligodendroglia or myelin components. Virus‐induced inflammation may be associated with the processing of myelin or oligodendroglial components and their presentation to the host's own T cell compartment. Alternatively, antigenic epitopes derived from the viral proteins may exhibit sufficient homology to host components that the immune response to the virus activates autoreactive T cells, i.e. molecular mimicry. Although it is not clear that each of these potential mechanisms participates in the pathogenesis of human demyelinating disease, analysis of the diverse demyelinating viral infections of both humans and rodents provides examples of many of these potential mechanisms. url: https://www.ncbi.nlm.nih.gov/pubmed/11145206/ doi: 10.1111/j.1750-3639.2001.tb00384.x id: cord-330553-sukrjl22 author: Stonedahl, Sarah title: The Role of Microglia during West Nile Virus Infection of the Central Nervous System date: 2020-08-28 words: 5545.0 sentences: 283.0 pages: flesch: 41.0 cache: ./cache/cord-330553-sukrjl22.txt txt: ./txt/cord-330553-sukrjl22.txt summary: WNV infection also induces neuroinflammation characterized by activation of innate immune cells, including microglia and astrocytes, production of inflammatory cytokines, breakdown of the blood-brain barrier, and infiltration of peripheral leukocytes. In this review, we will discuss the role of microglia in WNV-induced CNS disease as a contributor both to the protective innate immune response and to the development of long-term neurological damage. Inhibition of these chemokines/cytokines following treatment with minocycline resulted in decreased neuronal cell death following WNV infection of ex vivo spinal cord slice cultures [42] , suggesting they contribute to disease; however, depletion of microglia did not significantly change chemokine/cytokine expression in the brains of WNV-infected mice [60] so it is unclear what role microglia play in the production of these proteins. Death Receptor-Mediated Apoptotic Signaling Is Activated in the Brain following Infection with West Nile Virus in the Absence of a Peripheral Immune Response abstract: Encephalitis resulting from viral infections is a major cause of hospitalization and death worldwide. West Nile Virus (WNV) is a substantial health concern as it is one of the leading causes of viral encephalitis in the United States today. WNV infiltrates the central nervous system (CNS), where it directly infects neurons and induces neuronal cell death, in part, via activation of caspase 3-mediated apoptosis. WNV infection also induces neuroinflammation characterized by activation of innate immune cells, including microglia and astrocytes, production of inflammatory cytokines, breakdown of the blood-brain barrier, and infiltration of peripheral leukocytes. Microglia are the resident immune cells of the brain and monitor the CNS for signs of injury or pathogens. Following infection with WNV, microglia exhibit a change in morphology consistent with activation and are associated with increased expression of proinflammatory cytokines. Recent research has focused on deciphering the role of microglia during WNV encephalitis. Microglia play a protective role during infections by limiting viral growth and reducing mortality in mice. However, it also appears that activated microglia are triggered by T cells to mediate synaptic elimination at late times during infection, which may contribute to long-term neurological deficits following a neuroinvasive WNV infection. This review will discuss the important role of microglia in the pathogenesis of a neuroinvasive WNV infection. Knowledge of the precise role of microglia during a WNV infection may lead to a greater ability to treat and manage WNV encephalitis. url: https://www.ncbi.nlm.nih.gov/pubmed/32872152/ doi: 10.3390/vaccines8030485 id: cord-002757-upwe0cpj author: Sullivan, Kathleen E. title: Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies date: 2017-08-07 words: 24212.0 sentences: 1364.0 pages: flesch: 40.0 cache: ./cache/cord-002757-upwe0cpj.txt txt: ./txt/cord-002757-upwe0cpj.txt summary: The first section addresses general considerations, the second section profiles specific infections organized according to mechanism of transmission, and the third section focuses on unique phenotypes and unique susceptibilities in patients with PIDDs. This review does not address most parasitic diseases. In developing countries where polio is still endemic and oral polio vaccine is essential for eradicating the disease, it is of utmost importance that all PIDD patients and family members should not receive live oral polio (OPV) because of the reported prolonged excretion of the virus for months and even years [24] . As for host factors, although severe and fatal cases have been described in healthy immunocompetent hosts [129, 130] , there is evidence to suggest that children under the age of 10 [130] and immunocompromised hosts either secondary to hematologic malignancies, immunosuppressant treatment for organ transplantation, or HIV infection are at a greater risk to develop more severe disease with higher case fatality rates [131, 132] . abstract: In today’s global economy and affordable vacation travel, it is increasingly important that visitors to another country and their physician be familiar with emerging infections, infections unique to a specific geographic region, and risks related to the process of travel. This is never more important than for patients with primary immunodeficiency disorders (PIDD). A recent review addressing common causes of fever in travelers provides important information for the general population Thwaites and Day (N Engl J Med 376:548-560, 2017). This review covers critical infectious and management concerns specifically related to travel for patients with PIDD. This review will discuss the context of the changing landscape of infections, highlight specific infections of concern, and profile distinct infection phenotypes in patients who are immune compromised. The organization of this review will address the environment driving emerging infections and several concerns unique to patients with PIDD. The first section addresses general considerations, the second section profiles specific infections organized according to mechanism of transmission, and the third section focuses on unique phenotypes and unique susceptibilities in patients with PIDDs. This review does not address most parasitic diseases. Reference tables provide easily accessible information on a broader range of infections than is described in the text. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693703/ doi: 10.1007/s10875-017-0426-2 id: cord-334499-fz7vrnb1 author: Templeton, Steven P. title: Pathogenesis of acute and chronic central nervous system infection with variants of mouse hepatitis virus, strain JHM date: 2007-06-01 words: 6288.0 sentences: 297.0 pages: flesch: 37.0 cache: ./cache/cord-334499-fz7vrnb1.txt txt: ./txt/cord-334499-fz7vrnb1.txt summary: Infection of mice with variants of mouse hepatitis virus, strain JHM (MHV-JHM), provide models of acute and chronic viral infection of the central nervous system (CNS). Partially protective anti-viral immune responses may result in persistent infection and chronic demyelinating disease characterized by myelin removal from axons of the CNS and associated with dense macrophage/microglial infiltration. Demyelinating disease during MHV-JHM infection is immune-mediated, as mice that lack T lymphocytes fail to develop disease despite succumbing to encephalitis with high levels of infectious virus in the CNS. Demyelinating disease induced during MHV-JHM infection is partly immune mediated, as mice lacking the ability to generate T cell responses fail to develop demyelination, despite high viral loads and widespread inflammation in the CNS of infected mice [19, 20] . Further studies involve introduction of other chemoattractants into recombinant MHV-JHM, to evaluate their role in demyelinating disease, cell recruitment, generation of immune responses, and clearance of infectious virus in MHV-JHM-infected mice. abstract: Infection of mice with variants of mouse hepatitis virus, strain JHM (MHV-JHM), provide models of acute and chronic viral infection of the central nervous system (CNS). Through targeted recombination and reverse genetic manipulation, studies of infection with MHV-JHM variants have identified phenotypic differences and examined the effects of these differences on viral pathogenesis and anti-viral host immune responses. Studies employing recombinant viruses with a modified spike (S) glycoprotein of MHV-JHM have identified the S gene as a major determinant of neurovirulence. However, the association of S gene variation and neurovirulence with host ability to generate anti-viral CD8 T cell responses is not completely clear. Partially protective anti-viral immune responses may result in persistent infection and chronic demyelinating disease characterized by myelin removal from axons of the CNS and associated with dense macrophage/microglial infiltration. Demyelinating disease during MHV-JHM infection is immune-mediated, as mice that lack T lymphocytes fail to develop disease despite succumbing to encephalitis with high levels of infectious virus in the CNS. However, the presence of T lymphocytes or anti-viral antibody can induce disease in infected immunodeficient mice. The mechanisms by which these immune effectors induce demyelination share an ability to activate and recruit macrophages and microglia, thus increasing the putative role of these cells in myelin destruction. url: https://www.ncbi.nlm.nih.gov/pubmed/17917063/ doi: 10.1007/s12026-007-0079-y id: cord-299967-90aknp7c author: Terry, Rachael L title: Inflammatory monocytes and the pathogenesis of viral encephalitis date: 2012-12-17 words: 6111.0 sentences: 327.0 pages: flesch: 35.0 cache: ./cache/cord-299967-90aknp7c.txt txt: ./txt/cord-299967-90aknp7c.txt summary: Monocytes are a heterogeneous population of bone marrow-derived cells that are recruited to sites of infection and inflammation in many models of human diseases, including those of the central nervous system (CNS). Ly6C(hi)/CCR2(hi) inflammatory monocytes have been identified as the circulating precursors of brain macrophages, dendritic cells and arguably microglia in experimental autoimmune encephalomyelitis; Alzheimer''s disease; stroke; and more recently in CNS infection caused by Herpes simplex virus, murine hepatitis virus, Theiler''s murine encephalomyelitis virus, Japanese encephalitis virus and West Nile virus. Competitive and non-competitive glutamate receptor antagonists promote survival during neurovirulent Sindbis virus encephalitis [35, 36] and improved outcomes during coronavirus encephalitis [37] ↑ neuronal damage/ death ↑ production of NO/ ROS Reviewed in [38] BBB blood brain barrier; CNS central nervous system; HSV herpes simplex virus; MDP macrophage/dendritic cell precursor; MHV murine hepatitis virus; MMP matrix metalloproteinases; NO nitric oxide; NOS2 nitric oxide synthase-2; ROS reactive oxygen species; TMEV Theiler''s murine encephalomyelitis virus; WNV West Nile virus. abstract: Monocytes are a heterogeneous population of bone marrow-derived cells that are recruited to sites of infection and inflammation in many models of human diseases, including those of the central nervous system (CNS). Ly6C(hi)/CCR2(hi) inflammatory monocytes have been identified as the circulating precursors of brain macrophages, dendritic cells and arguably microglia in experimental autoimmune encephalomyelitis; Alzheimer’s disease; stroke; and more recently in CNS infection caused by Herpes simplex virus, murine hepatitis virus, Theiler’s murine encephalomyelitis virus, Japanese encephalitis virus and West Nile virus. The precise differentiation pathways and functions of inflammatory monocyte-derived populations in the inflamed CNS remains a contentious issue, especially in regard to the existence of monocyte-derived microglia. Furthermore, the contributions of monocyte-derived subsets to viral clearance and immunopathology are not well-defined. Thus, understanding the pathways through which inflammatory monocytes migrate to the brain and their functional capacity within the CNS is critical to inform future therapeutic strategies. This review discusses some of the key aspects of inflammatory monocyte trafficking to the brain and addresses the role of these cells in viral encephalitis. url: https://doi.org/10.1186/1742-2094-9-270 doi: 10.1186/1742-2094-9-270 id: cord-292255-zafnq8gl author: Trojano, M. title: Chapter 8 Environmental Factors and Their Regulation of Immunity in Multiple Sclerosis date: 2016-12-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract In multiple sclerosis (MS), environmental factors and genetic traits cooperate in the induction of the chronic activation of immune cells to produce the brain pathology. Epidemiology has focused on different environmental risk factors but certainly virus infection, smoking, vitamin D levels, and sunlight exposure are the most relevant. What is certainly less clear is the way in which these external factors are able to induce and sustain the internal pathology process of the disease. Epigenetics has been recently focused on trying to shed light on this aspect. As a matter of fact epigenetic changes are highly sensitive to environmental factors that therefore may influence the susceptibility to the disease by acting through epigenetic modifications. In this chapter we discuss the most relevant environmental factors and how they may affect the immune response in MS. Finally, we discuss the possible role of the microbiota in inducing autoimmunity in MS. url: https://api.elsevier.com/content/article/pii/B9780128019146000088 doi: 10.1016/b978-0-12-801914-6.00008-8 id: cord-299051-5r2s8z1a author: Tsuhako, Maria Heloisa title: Tempol ameliorates murine viral encephalomyelitis by preserving the blood–brain barrier, reducing viral load, and lessening inflammation date: 2010-03-01 words: 5935.0 sentences: 308.0 pages: flesch: 44.0 cache: ./cache/cord-299051-5r2s8z1a.txt txt: ./txt/cord-299051-5r2s8z1a.txt summary: Furthermore, treatment with tempol decreased CNS viral titers, macrophage and T lymphocyte infiltration, and levels of markers of inflammation, such as expression of inducible nitric oxide synthase, transcription of tumor necrosis factor-α and interferon-γ, and protein nitration. Immunohistochemical analysis of the brain (Fig. 6 ) and spinal cord (data not shown) tissues showed that viral infection resulted in macrophage infiltration, iNOS expression, and protein nitration, all of which were greatly attenuated by tempol treatment. Semiquantitative image analysis of the immunostaining of the brain tissues revealed that treatment with tempol reduced macrophage infiltration, iNOS expression, and 3nitrotyrosine levels to about 4, 26, and 16% of those of untreated mice, respectively (Fig. 7A) . In comparison, tempol is more effective than uric acid in scavenging nitric oxide-derived oxidants [9] , displays low toxicity in animal models [15, 16] , permeates the blood-brain barrier (Fig. 2) , and inhibits the enzyme myeloperoxidase ( [20] ; see Augusto et al., [53] , which has been recently associated with MS [54, 55] . abstract: Multiple sclerosis (MS) is a progressive inflammatory and/or demyelinating disease of the human central nervous system (CNS). Most of the knowledge about the pathogenesis of MS has been derived from murine models, such as experimental autoimmune encephalomyelitis and viral encephalomyelitis. Here, we infected female C57BL/6 mice with a neurotropic strain of the mouse hepatitis virus (MHV-59A) to evaluate whether treatment with the multifunctional antioxidant tempol (4-hydroxy-2,2,6,6-tetramethyl-1-piperidinyloxy) affects the ensuing encephalomyelitis. In untreated animals, neurological symptoms developed quickly: 90% of infected mice died 10 days after virus inoculation and the few survivors presented neurological deficits. Treatment with tempol (24 mg/kg, ip, two doses on the first day and daily doses for 7 days plus 2 mM tempol in the drinking water ad libitum) profoundly altered the disease outcome: neurological symptoms were attenuated, mouse survival increased up to 70%, and half of the survivors behaved as normal mice. Not surprisingly, tempol substantially preserved the integrity of the CNS, including the blood–brain barrier. Furthermore, treatment with tempol decreased CNS viral titers, macrophage and T lymphocyte infiltration, and levels of markers of inflammation, such as expression of inducible nitric oxide synthase, transcription of tumor necrosis factor-α and interferon-γ, and protein nitration. The results indicate that tempol ameliorates murine viral encephalomyelitis by altering the redox status of the infectious environment that contributes to an attenuated CNS inflammatory response. Overall, our study supports the development of therapeutic strategies based on nitroxides to manage neuroinflammatory diseases, including MS. url: https://www.sciencedirect.com/science/article/pii/S0891584909007849 doi: 10.1016/j.freeradbiomed.2009.12.013 id: cord-280987-uhxk5b1b author: Turtle, L. title: Encephalitis, Viral date: 2014-05-01 words: 2266.0 sentences: 120.0 pages: flesch: 33.0 cache: ./cache/cord-280987-uhxk5b1b.txt txt: ./txt/cord-280987-uhxk5b1b.txt summary: Encephalitis is inflammation and swelling of the brain, often caused by an acute viral infection, or a paraor postinfectious phenomenon known as acute disseminated encephalomyelitis (ADEM). The term includes both viral infections of the brain with predominantly gray matter disease and acute disseminated encephalomyelitis (ADEM), an immune-mediated demyelinating disease. Clinically, acute viral encephalitis and ADEM usually manifest with fever, severe headache, neck stiffness, alterations of consciousness, focal neurological signs, and often seizures, especially in children. Once permissive host cells are infected in the subcutaneous tissue, the mucous membranes, or the hematopoietic system (particularly macrophages), viruses replicate usually locally before there is invasion of the central nervous system (CNS). Enteroviruses and mumps virus infect primarily meningeal and ependymal cells; therefore, they usually cause benign meningitis and only rarely are associated with encephalitis. On rare occasions when arboviruses infect the brain, they usually cause encephalitis with a significant death rate; thus, these viruses are not highly neuroinvasive but are highly neurotropic (and neuronotropic) and neurovirulent. abstract: Encephalitis is inflammation and swelling of the brain, often caused by an acute viral infection, or a para- or postinfectious phenomenon known as acute disseminated encephalomyelitis (ADEM). The most common sporadic viral cause is herpes simplex virus, but arthropodborne viruses, such as Japanese encephalitis virus, are a major cause in some settings, and rabies in others. Herpes simplex encephalitis is treated with acyclovir; rabies and Japanese encephalitis are preventable with vaccines. With the reduction in measles through vaccination, the incidence of ADEM, which often follows measles, has also reduced. url: https://api.elsevier.com/content/article/pii/B9780123851574003754 doi: 10.1016/b978-0-12-385157-4.00375-4 id: cord-010016-fs8pjy1z author: WEBB, H. E. title: CAN VIRAL ENVELOPE GLYCOLIPIDS PRODUCE AUTO‐IMMUNITY, WITH REFERENCE TO THE CNS AND MULTIPLE SCLEROSIS? date: 2008-05-12 words: 2976.0 sentences: 154.0 pages: flesch: 47.0 cache: ./cache/cord-010016-fs8pjy1z.txt txt: ./txt/cord-010016-fs8pjy1z.txt summary: In this paper it is proposed that CNS demyelination could arise in susceptible individuals (HLA type) from an immune response to glycolipids, triggered by the carrier effect of one or more enveloped neurotropic viruses. The demyelination is dependent upon T-lymphocytes probably cytotoxic cells (Jagelman et al., 1978; Fazakerley, Amor & Webb 1983; Pathak et al., 1983) and probably results from an immune reaction against viral antigens on the surface of oligodendrocytes or myelin. Since all are budding viruses they will have a similar host derived viral envelope provided the virus replicates in the same cell type. It is an intriguing possibility that CNS demyelination in diseases such as MS, arises as a result of an auto-immune reaction against specific glycolipids, induced by the carrier effect of a budding neurotropic virus. I n this way any number of enveloped neurotropic viruses could be involved in initiating and restimulating a n autoimmune response to the same brain cell membrane specific glycolipid(s). abstract: Many viruses, with lipid envelopes derived from the host cell membranes, have been implicated in the aetiology of multiple sclerosis (MS), and epidemiological studies support an infectious agent. Alternatively the disease is thought by other workers to be auto‐immune in nature, and recently much attention has been focused on immunological sensitivity to glycolipids in MS patients. In this paper it is proposed that CNS demyelination could arise in susceptible individuals (HLA type) from an immune response to glycolipids, triggered by the carrier effect of one or more enveloped neurotropic viruses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168014/ doi: 10.1111/j.1365-2990.1984.tb00335.x id: cord-329750-purunxce author: Waldman, Amy title: Childhood multiple sclerosis: A review date: 2006-06-28 words: 8430.0 sentences: 481.0 pages: flesch: 49.0 cache: ./cache/cord-329750-purunxce.txt txt: ./txt/cord-329750-purunxce.txt summary: Although children and adults with MS have similar neurological symptoms, laboratory (cerebrospinal fluid) data, and neuroimaging findings, the clinical course, pathogenesis, and treatment of childhood onset MS require further investigation. The study concluded that children and adults with MS have similar clinical profiles, including mode of onset, symptoms, and physical and laboratory (cerebral spinal fluid [CSF]) findings. The results from the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) and Safety and Efficacy of Natalizumab in Combination with Interferon ␤-1a in Patients with Relapsing Remitting Multiple Sclerosis (SENTINEL) studies in adult patients indicate that the annualized rate of clinical relapses was reduced by 68%, the number of new and enhancing MRI lesions was reduced by 83%, and a decrease occurred in progression and prolongation of the interval before neurological deterioration, demonstrating the usefulness of the drug [Polman et al., 2006; Rudicket al., 2006] . abstract: Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS) that is increasingly recognized as a disease that affects children. Similar to adult‐onset MS, children present with visual and sensory complaints, as well as weakness, spasticity, and ataxia. A lumbar puncture can be helpful in diagnosing MS when CSF immunoglobulins and oligoclonal bands are present. White matter demyelinating lesions on MRI are required for the diagnosis; however, children typically have fewer lesions than adults. Many criteria have been proposed to diagnose MS that have been applied to children, mostly above 10 years of age. The recent revisions to the McDonald criteria allow for earlier diagnosis, such as after a clinically isolated event. However, children are more likely than adults to have monosymptomatic illnesses. None of the approved disease‐modifying therapies used in adult‐onset MS have been approved for pediatrics; however, a few studies have verified their safety and tolerability in children. Although children and adults with MS have similar neurological symptoms, laboratory (cerebrospinal fluid) data, and neuroimaging findings, the clinical course, pathogenesis, and treatment of childhood onset MS require further investigation. MRDD Research Reviews 2006;12:147–156. © 2006 Wiley‐Liss, Inc. url: https://www.ncbi.nlm.nih.gov/pubmed/16807911/ doi: 10.1002/mrdd.20105 id: cord-272981-8gahvdt0 author: Wege, Helmut title: Relapsing subacute demyelinating encephalomyelitis in rats during the course of coronavirus JHM infection date: 1984-08-31 words: 3725.0 sentences: 295.0 pages: flesch: 57.0 cache: ./cache/cord-272981-8gahvdt0.txt txt: ./txt/cord-272981-8gahvdt0.txt summary: These results demonstrate that mutants of JHM virus can induce a relapsing demyelinating disease process, associated with a persistent infection, which possesses some similarities to chronic experimental allergic encephalomyelitis. It has been shown that an autoimmune reaction against CNS tissue can lead to 6hronic relapsing demyelination as seen in chronic experimental allergic encephalomyelitis (EAE) whereas the role of a virus infection in the induction of such a condition has not so far been directly demonstrated (McFarlin et al. After virus infection in rats inflammatory disseminating CNS lesions of marked demyelination develop accompanied by clinical signs of a subacute disease after varying incubation times. The induction of a progressive demyelinating, or relapsing demyelinating, disease process, in JHM virus-infected rats has ~me parallels to chronic EAE, an animal model based on sensitation ~8ainst CNS tissue extracts or myelin basic protein (McFarlin et al. abstract: Abstract Temperature-sensitive mutants of the murine coronavirus JHM induced a subacute demyelinating encephalomyelitis (SDE) in young rats. Neurological symptoms were associated with marked lesions of primary demyelination in the white matter of the central nervous system (CNS), and developing after an incubation time of several weeks to months. Many rats survived this infection and recovered completely from this CNS disease. Among 43 survivors of SDE, 9 rats developed a relapse 27–153 days after onset of the first attack. Neuropathological examination of these animals revealed areas of fresh demyelination together with old remyelinated lesions. Viral antigens were detectable in the neighbourhood of fresh lesions and in some cases infectious virus was re-isolated from rats revealing low antibody titers to JHM virus. These results demonstrate that mutants of JHM virus can induce a relapsing demyelinating disease process, associated with a persistent infection, which possesses some similarities to chronic experimental allergic encephalomyelitis. url: https://www.sciencedirect.com/science/article/pii/0165572884900225 doi: 10.1016/0165-5728(84)90022-5 id: cord-332109-ont0tqpn author: Wei, Yufeng title: Substance Use Disorder in the COVID-19 Pandemic: A Systematic Review of Vulnerabilities and Complications date: 2020-07-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: As the world endures the coronavirus disease 2019 (COVID-19) pandemic, the conditions of 35 million vulnerable individuals struggling with substance use disorders (SUDs) worldwide have not received sufficient attention for their special health and medical needs. Many of these individuals are complicated by underlying health conditions, such as cardiovascular and lung diseases and undermined immune systems. During the pandemic, access to the healthcare systems and support groups is greatly diminished. Current research on COVID-19 has not addressed the unique challenges facing individuals with SUDs, including the heightened vulnerability and susceptibility to the disease. In this systematic review, we will discuss the pathogenesis and pathology of COVID-19, and highlight potential risk factors and complications to these individuals. We will also provide insights and considerations for COVID-19 treatment and prevention in patients with SUDs. url: https://doi.org/10.3390/ph13070155 doi: 10.3390/ph13070155 id: cord-315656-asvf4roo author: Wu, Junjiao title: Revisiting the Immune Balance Theory: A Neurological Insight Into the Epidemic of COVID-19 and Its Alike date: 2020-10-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: As the pandemic of COVID-19 is raging around the world, the mysteriousness of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) coronavirus is being revealed by the concerted endeavors of scientists. Although fever and pneumonia are typical symptoms, COVID-19 patients exhibit multiple neurological complications. In this interim review, we will summarize the neurological manifestations and their potential causes in COVID-19. Similar to the other two fatal respiratory coronaviruses, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 also shows to be neuroinvasive that may spread from the periphery to brain, probably by the retrograde axonal transport. The invaded viruses may directly disrupt the complex neural circuits, and raise a chronic activation of immune responses. In another hand, multiple organ failure in severe COVID-19 is caused by the systemic acute immune responses, and unsurprisingly caused the brain inflammation and led to encephalitis. However, in the central nervous system (CNS), the activation of resident immune cells including microglia and astrocytes may lead to chronic immune imbalance, which underlies the potential long-term effects in synaptic changes and neuropsychiatric impairments. The neuroinvasive biology also provides a possible link with the Braak staging of neurodegenerative diseases such as Parkinson's disease (PD). Although with considerable advances, the neurotropic potential and chronic neurological effects caused by SARS-CoV-2 infections merit further investigations. url: https://doi.org/10.3389/fneur.2020.566680 doi: 10.3389/fneur.2020.566680 id: cord-317651-lsca8vt2 author: Yong, V. Wee title: Metalloproteinases in biology and pathology of the nervous system date: 2001 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Matrix metalloproteinases (MMPs) have been implicated in several diseases of the nervous system. Here we review the evidence that supports this idea and discuss the possible mechanisms of MMP action. We then consider some of the beneficial functions of MMPs during neural development and speculate on their roles in repair after brain injury. We also introduce a family of proteins known as ADAMs (a disintegrin and metalloproteinase), as some of the properties previously ascribed to MMPs are possibly the result of ADAM activity. url: https://www.ncbi.nlm.nih.gov/pubmed/11433375/ doi: 10.1038/35081571 id: cord-016954-l3b6n7ej author: Young, Colin R. title: Animal Models of Multiple Sclerosis date: 2008 words: 9705.0 sentences: 495.0 pages: flesch: 44.0 cache: ./cache/cord-016954-l3b6n7ej.txt txt: ./txt/cord-016954-l3b6n7ej.txt summary: The relative inaccessibility and sensitivity of the central nervous system (CNS) in humans preclude studies on disease pathogenesis, and so much of our understanding of infections and immune responses has been derived from experimental animal models. Viral models are immensely relevant since epidemiological studies suggest an environmental factor, and almost all naturally occurring CNS demyelinating diseases of humans and animals of known etiology are caused by a virus. The most widely studied models of MS are the experimental infections of rodents resulting in an inflammatory demyelinating disease in the CNS, such as Theiler''s virus, mouse hepatitis virus, and Semliki Forest virus. Theiler''s virus-induced demyelination, a model for human MS, bears several similarities to the human disease: an immune-mediated demyelination, involvement of CD4 + helper T cells and CD8 + cytotoxic T cells, delayed type hypersensitivity responses to viral antigens and autoantigens, and pathology. abstract: To determine whether an immunological or pharmaceutical product has potential for therapy in treating multiple sclerosis (MS), detailed animal models are required. To date many animal models for human MS have been described in mice, rats, rabbits, guinea pigs, marmosets, and rhesus monkeys. The most comprehensive studies have involved murine experimental allergic (or autoimmune) encephalomyelitis (EAE), Semliki Forest virus (SFV), mouse hepatitis virus (MHV), and Theiler’s murine encephalomyelitis virus (TMEV). Here, we describe in detail multispecies animal models of human MS, namely EAE, SFV, MHV, and TMEV, in addition to chemically induced demyelination. The validity and applicability of each of these models are critically evaluated. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121393/ doi: 10.1007/978-1-59745-285-4_69 id: cord-252569-9rv1p3qh author: Zanella, M.-C. title: High-throughput sequencing for the aetiologic identification of viral encephalitis, meningoencephalitis, and meningitis. A narrative review and clinical appraisal date: 2019-01-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Viral aetiologies are the most common cause of central nervous system (CNS) infections. Approximately one-half of CNS infections remain of undetermined origin. High-throughput sequencing (HTS) brought new perspectives to CNS infection investigations, allowing investigation of viral aetiologies with an unbiased approach. HTS use is still limited to specific clinical situations. OBJECTIVES: The aim of this review was to evaluate the contribution and pitfalls of HTS for the aetiologic identification of viral encephalitis, meningoencephalitis, and meningitis in CNS patient samples. SOURCES: PubMed was searched from 1 January 2008 to 2 August 2018 to retrieve available studies on the topic. Additional publications were included from a review of full-text sources. CONTENT: Among 366 studies retrieved, 29 used HTS as a diagnostic technique. HTS was performed in cerebrospinal fluid and brain biopsy samples of 307 patients, including immunocompromised, immunocompetent paediatric, and adult cases. HTS was performed retrospectively in 18 studies and prospectively in 11. HTS led to the identification of a potential causal virus in 41 patients, with 11 viruses known and ten not expected to cause CNS infections. Various HTS protocols were used. IMPLICATIONS: The additional value of HTS is difficult to quantify because of various biases. Nevertheless, HTS led to the identification of a viral cause in 13% of encephalitis, meningoencephalitis, and meningitis cases in which various assays failed to identify the cause. HTS should be considered early in clinical management as a complement to routine assays. Standardized strategies and systematic studies are needed for the integration of HTS in clinical management. url: https://www.sciencedirect.com/science/article/pii/S1198743X18308127 doi: 10.1016/j.cmi.2018.12.022 id: cord-003738-el0wyu74 author: Zhang, Qingxiu title: The interleukin-4/PPARγ signaling axis promotes oligodendrocyte differentiation and remyelination after brain injury date: 2019-06-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The repair of white matter damage is of paramount importance for functional recovery after brain injuries. Here, we report that interleukin-4 (IL-4) promotes oligodendrocyte regeneration and remyelination. IL-4 receptor expression was detected in a variety of glial cells after ischemic brain injury, including oligodendrocyte lineage cells. IL-4 deficiency in knockout mice resulted in greater deterioration of white matter over 14 d after stroke. Consistent with these findings, intranasal delivery of IL-4 nanoparticles after stroke improved white matter integrity and attenuated long-term sensorimotor and cognitive deficits in wild-type mice, as revealed by histological immunostaining, electron microscopy, diffusion tensor imaging, and electrophysiology. The selective effect of IL-4 on remyelination was verified in an ex vivo organotypic model of demyelination. By leveraging primary oligodendrocyte progenitor cells (OPCs), microglia-depleted mice, and conditional OPC-specific peroxisome proliferator-activated receptor gamma (PPARγ) knockout mice, we discovered a direct salutary effect of IL-4 on oligodendrocyte differentiation that was mediated by the PPARγ axis. Our findings reveal a new regenerative role of IL-4 in the central nervous system (CNS), which lies beyond its known immunoregulatory functions on microglia/macrophages or peripheral lymphocytes. Therefore, intranasal IL-4 delivery may represent a novel therapeutic strategy to improve white matter integrity in stroke and other brain injuries. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6608986/ doi: 10.1371/journal.pbio.3000330 id: cord-353812-4oxbczqe author: Zoghi, Anahita title: A case of possible atypical demyelinating event of the central nervous system following COVID-19 date: 2020-06-24 words: 1543.0 sentences: 99.0 pages: flesch: 47.0 cache: ./cache/cord-353812-4oxbczqe.txt txt: ./txt/cord-353812-4oxbczqe.txt summary: Some COVID-19 patients, especially those suffering from a severe disease, are highly likely to have central nervous system (CNS) manifestations. It has been shown that severe infection with SARS-CoV-2 is associated with neurological manifestations such as headache, epilepsy, cerebrovascular events, and encephalitis (Bohmwald et al. Studies on SARS-CoV-1 revealed a delayed self-reactive T-cell suppression due to viral replication, which leads to neuroinflammation, demyelination or axonal damage of the CNS (Savarin et al., 2017 . Recent studies have shown that the novel coronavirus appears to cross the blood-brain barrier and cause acute or delayed CNS demyelination or axonal damage (Desforges et al., 2020) . Moreover, a recent report revealed that CNS delayed demyelinating events following COVID-19 . Severe COVID-19 may affect the CNS and have various acute or delayed neurological complications. During the COVID-19 pandemic, it is important to consider SARS-CoV-2 infection when seeing patients with neurological manifestations, especially those needing immune-modulator therapy, since the established recommendations are insufficient at this time. abstract: After the novel coronavirus disease outbreak first began in Wuhan, China, in December 2019, the viral epidemic has quickly spread across the world, and it is now a major public health concern. Here we present a 21-year-old male with encephalomyelitis following intermittent vomiting and malaise for 4 days. He reported upper respiratory signs and symptoms 2 weeks before this presentation. Two cerebrospinal fluid (CSF) analyses were notable for mononuclear pleocytosis, elevated protein (more than 100 mg/dl), and hypoglycorrhachia. Brain Magnetic Resonance Imaging (MRI) showed bilateral posterior internal capsule lesions extending to the ventral portion of the pons and a marbled splenium hyperintensity pattern. Cervical and thoracic MRI showed longitudinally extensive transverse myelitis (LETM), none of which were enhanced with gadolinium. Both the AQP4 and MOG antibodies were negative. Spiral chest computed tomography (CT) scan confirmed to COVID-19 as did the high IgG level against coronavirus, but the oropharyngeal swabs were negative. Neurological manifestations of COVID-19 have not been adequately studied. Some COVID-19 patients, especially those suffering from a severe disease, are highly likely to have central nervous system (CNS) manifestations. Our case is a post-COVID-19 demyelinating event in the CNS. url: https://api.elsevier.com/content/article/pii/S2211034820304004 doi: 10.1016/j.msard.2020.102324 id: cord-006824-btcdjmfp author: nan title: Key Note and State of the Art Lectures date: 2002-09-07 words: 7577.0 sentences: 377.0 pages: flesch: 34.0 cache: ./cache/cord-006824-btcdjmfp.txt txt: ./txt/cord-006824-btcdjmfp.txt summary: In a prospective phase II trial, we treated 37 patients with high dose therapy and autologous bone marrow transplantation for follicular lymphoma in first complete or partial remission [6] . A comparison with similar autologous HCT recipients with NHL who had not been treated with the monoclonal antibody after transplantation indicates that Figure 1 : Overall survival, event-free survival and relapse following autologous bone marrow transplantation in 37 patients with follicular lymphoma during their first complete or first partial chemotherapy-induced remissions this new post-transplant therapy has contributed positively to the treatment outcome. In 1986, a first group of 17 patients (14 with NHL and three with Hodgkin''s disease) was described indicating that extended disease-free long-term survival can be attained with high dose therapy followed by allogeneic transplantation utilizing hematopoietic cells obtained either from fully or closely matched related donors [9] . abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103144/ doi: 10.1007/s00277-002-0513-0 id: cord-009997-oecpqf1j author: nan title: 2018 ASPHO ABSTRACTS date: 2018-03-31 words: 182060.0 sentences: 10342.0 pages: flesch: 48.0 cache: ./cache/cord-009997-oecpqf1j.txt txt: ./txt/cord-009997-oecpqf1j.txt summary: Completed cranial radiation and proceeded to allogeneic stem cell transplant with unrelated cord marrow donor and is disease free at approximately day +200.Case 2: 5 year-old female diagnosed with FLT3 and MLL negative AML and completed treatment per COG AAML1031 study on the low risk arm without Bortezomib. Design/Method: This study was a retrospective chart review that included patients 3 to 23 years old with sickle cell disease type SS and S 0 followed at St. Christopher''s Hospital for Children. Background: Hydroxyurea, chronic blood transfusion, and bone marrow transplantation can reduce complications, and improve survival in sickle cell disease (SCD), but are associated with a significant decisional dilemma because of the inherent risk-benefit tradeoffs, and the lack of comparative studies. Brown University -Hasbro Children''s Hospital, Providence, Rhode Island, United States Background: Despite clinical advances in the treatment of sickle cell disease (SCD) in pediatric and young adult patients, pain remains a significant source of disease-related morbidity. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167873/ doi: 10.1002/pbc.27057 id: cord-015352-2d02eq3y author: nan title: ESPR 2017 date: 2017-04-26 words: 82253.0 sentences: 4479.0 pages: flesch: 46.0 cache: ./cache/cord-015352-2d02eq3y.txt txt: ./txt/cord-015352-2d02eq3y.txt summary: Lapierre; Montreal/CA Summary: Objectives: To review the classification of visceroatrial situs To describe the associated cardiac and non-cardiac anomalies To illustrate typical findings in fetuses, neonates and children To discuss the surgical consideration and the long-term follow-up in these patients Abstract: By definition, the type of situs is determined by the relationship between the atria and the adjacent organs. As is often the case, radiology in JIA is all about: knowing your clinicians (i.e. the pretest likelihood for disease) being technically eloquent (e.g. using high-resolution US probes, not delaying post-contrast MRI acquisitions) knowing what is normal (e.g. normal undulations in the articular surface, focal bone marrow signal variation) not being dogmatic about individual observations or measurements interpreting your findings in a clinical context The lecture will demonstrate similarities and differences among joints and modalities in children with variable-severity JIA. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103096/ doi: 10.1007/s00247-017-3820-2 id: cord-018034-gx5c9mk8 author: nan title: Cell and Tissue Reactions date: 2006 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Similar types of tissue reaction result as a final common pathway from a wide array of different internal brain pathophysiological states and external insults. Since these cellular and tissue reactions are largely independent of the specific type of insults, they are, therefore, non-specific. The tissue reactions are to be differentiated according to their specific pathogenetic mechanisms, though these mechanisms as well as the phenomena are overlapping as demonstrated in Fig. 4.1; brain ischemia as a type of metabolic disturbance, edema, intracranial pressure, necrosis, herniation and inflammation are influencing themselves and are dependent on each other. Some will be mentioned again in later chapters as viewed from different forensic aspects; therefore, a certain redundancy is unavoidable. Immediately following, we offer a survey of the individual types of reaction and their fundamental pathophysiological principles and morphology. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122794/ doi: 10.1007/3-540-28995-x_4 id: cord-022659-chwk2bs4 author: nan title: Abstracts: Poster session date: 2004-10-08 words: 49153.0 sentences: 2598.0 pages: flesch: 49.0 cache: ./cache/cord-022659-chwk2bs4.txt txt: ./txt/cord-022659-chwk2bs4.txt summary: We investigated the usefulness of informant-based data in Alzheimer''s disease (AD) by comparing caregivers'' subjective evaluations of 83 probable A D patients'' performance on an abbreviated version of the Memory Self-Report Questionnaire to objective evaluations derived from an extensive battery of neuropsychological tests and to clinicians'' evaluations. Compared with 89 subjects (mean age 75.2 yr; 34 men, 55 women) with dementia of the Alzheimer type (DAT), there were no significant group differences for comparable Clinical Dementia Rating stages of dementia for measures of language, Activities of Daily Living, or general cognition. The mean age at onset did not differ significantly between handedness groups (F [ l,lOO] = .82), but the mean duration of symptoms ( Alterations in the optical properties of brain can be used to detect pathological changes in patients with Alzheimer''s disease (AD). abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159508/ doi: 10.1002/ana.410320224 id: cord-022756-kdgo4rqb author: nan title: Hematopoietic Tumors date: 2012-11-28 words: 42445.0 sentences: 2381.0 pages: flesch: 43.0 cache: ./cache/cord-022756-kdgo4rqb.txt txt: ./txt/cord-022756-kdgo4rqb.txt summary: Hepatosplenic lymphoma is a relatively uncommon, distinct presentation in the dog marked by a lack of significant peripheral lymphadenopathy in the face of hepatic, splenic, and bone marrow infiltration with malignant lymphocytes, usually of T-cell origin. In a randomized study of 60 dogs with lymphoma comparing CHOP-based chemotherapy with CHOPbased chemotherapy and a human granulocyte-macrophage colony-stimulating factor (GM-CSF) DNA cationic-lipid complexed autologous whole tumor cell vaccine, a small measure of immunomodulation was documented by delayed-type hypersensitivity; however, significant improvement in clinical outcome was not noted. 263 Total body irradiation (and/or ablative chemotherapy) for complete or partial bone marrow ablation followed by reconstitution with bone marrow or stem-cell transplant in dogs, although a recognized model in comparative research settings, 264,265 is still in its early phases of development and application in clinical veterinary It is associated with slow progression and long-term survival following corticosteroid management; however, it does have the potential to progress to high-grade lymphoma. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161412/ doi: 10.1016/b978-1-4377-2362-5.00032-3 id: cord-023026-2r84ndzv author: nan title: Posters date: 2013-06-14 words: 138458.0 sentences: 6513.0 pages: flesch: 40.0 cache: ./cache/cord-023026-2r84ndzv.txt txt: ./txt/cord-023026-2r84ndzv.txt summary: Thus, this work provides the basis to identify molecular pathways regulated by distinct niche/environmental signals and involved in the heterogeneity of adult OPCs. Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative demyelinating disease of the central nervous system (CNS) characterized by inflammation, which leads to formation of demyelinating areas due to loss of oligodendrocytes, astrogliosis and, finally, axonal degeneration. Taken together, these results demonstrate the important role of miR-200b in modulating the MAPK pathway via c-Jun which in turn affects different aspects of the inflammatory process accompanying microglia activation including cytokine response, NO production, phagocytosis and neuronal cell death. For this purpose, coronal cryostat free-floating sections from the brain of both adult transgenic mice and their corresponding wild-type (Wt) littermates, were processed for the study of astrocytes using GFAP immunohistochemistry and microglia using antibodies against Iba1 and several markers commonly related to the activated phenotype of these microglial cells, such as CD16/32 (Fc receptor), F4/80, CD11b, CD206, CD150 and MHC-II. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165910/ doi: 10.1002/glia.22530 id: cord-023143-fcno330z author: nan title: Molecular aspects of viral immunity date: 2004-02-19 words: 43425.0 sentences: 2056.0 pages: flesch: 47.0 cache: ./cache/cord-023143-fcno330z.txt txt: ./txt/cord-023143-fcno330z.txt summary: Based on a variety of experimental evidence, it is clear that demyelination induced in SJUJ mice by infection with the BeAn strain of TMEV is a Thl-mediated event: (a) disease induction is suppressed in T cell-deprived mice and by in vivo treatment with anti-I-A and anti-CD4 antibodies; (b) disease susceptibility correlates temporally with the development of TMEV-specific, MHC-class Il-restricted DTH responses and with a predominance of anti-viral lgG2a antibody; (c) activated (Le., lL-2RC) T cells infiltrating the CNS are exclusively of the CD4+ phenotype, and (d) proinflammatory cytokines (IFNq and TNF-p) are predominantly produced in the CNS. These results have important implications for a possible viral trigger in MS as they indicate that chronic demyelination in TMEV-infected mice is initiated in the absence of demonstrable neuroantigen-specific autoimmune responses and are consistent with a model wherein early myelin damage is mediated via primarily by mononuclear phagocytes recruited to the CNS and activated by pro-inflammatory cytokines produced by TMEV-specific Thl cells. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167094/ doi: 10.1002/jcb.240591009 id: cord-257167-rz4r5sj7 author: nan title: Abstracts for the 29th Annual Meeting of the Japan Neuroscience Society (Neuroscience2006) date: 2006-12-31 words: 240925.0 sentences: 13617.0 pages: flesch: 47.0 cache: ./cache/cord-257167-rz4r5sj7.txt txt: ./txt/cord-257167-rz4r5sj7.txt summary: SY1-3-11-3 SAD: A novel kinase implicated in phosphoproteome at the presynaptic active zone Toshihisa Ohtsuka Department of Clinical and Molecular Pathology, Faculty of Medicine/Graduate School of Medicine, University of Toyama, Toyama, Japan SAD is a serine/threonine kianse, which has been shown to regulate various neuronal functions during development, including clustering synaptic vesicles, maturation of synapses, and axon/dendrite polarization: these have recently been revealed by genetic studies in C. The results suggest that EAAT4 plays a major role in regulating the concentration of CF transmitters, possibly glutamate, in the route of its extrasynaptic diffusion, and determining the degree of CF-induced inhibition of GABA release from BCs depending on the regional difference of EAAT4 expression in postsynaptic PCs. Chitoshi Takayama 1 , Yoshiro Inoue 1 1 Department of Molecular Neuroanatomy, Hokkaido University School of Medicine, Sapporo, Japan GABA mediates inhibitory transmission in the adult central nervous system (CNS). abstract: nan url: https://api.elsevier.com/content/article/pii/S016801020600085X doi: 10.1016/j.neures.2006.04.004 id: cord-353298-vr5hnzp8 author: nan title: In vitro analysis of the oligodendrocyte lineage in mice during demyelination and remyelination date: 1990-09-01 words: 6929.0 sentences: 326.0 pages: flesch: 45.0 cache: ./cache/cord-353298-vr5hnzp8.txt txt: ./txt/cord-353298-vr5hnzp8.txt summary: Cultures from demyelinated tissue differed in several ways from those of age-matched controls: first, the total number of O-2A lineage cells was strikingly increased; second, the O-2A population consisted of a higher proportion of O4-positive astrocytes and cells of mixed oligodendrocyte-astrocyte phenotype; and third, all the cell types within the O-2A lineage showed enhanced proliferation. Cultures from demyelinated tissue differed in several ways from those of agematched controls: first, the total number of O-2A lin-cage cells was strikingly increased; second, the O-2A population consisted of a higher proportion of 04positive astrocytes and cells of mixed oligodendrocyteastrocyte phenotype; and third, all the cell types within the O-2A lineage showed enhanced proliferation. Since PDGF, IGF-I, and bFGF can each induce proliferation of neonatal O-2A progenitor cells in the developing rat CNS (reviewed in Dubois-Dalcq and Armstrong, 1990), we assayed the mitogenic effect of these growth factors in our cultures of adult mouse spinal cord (see protocol outlined in Fig. 1 C) . abstract: A demyelinating disease induced in C57B1/6N mice by intracranial injection of a coronavirus (murine hepatitis virus strain A59) is followed by functional recovery and efficient CNS myelin repair. To study the biological properties of the cells involved in this repair process, glial cells were isolated and cultured from spinal cords of these young adult mice during demyelination and remyelination. Using three-color immunofluorescence combined with [3H]thymidine autoradiography, we have analyzed the antigenic phenotype and mitotic potential of individual glial cells. We identified oligodendrocytes with an antibody to galactocerebroside, astrocytes with an antibody to glial fibrillary acidic protein, and oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells with the O4 antibody. Cultures from demyelinated tissue differed in several ways from those of age-matched controls: first, the total number of O-2A lineage cells was strikingly increased; second, the O-2A population consisted of a higher proportion of O4-positive astrocytes and cells of mixed oligodendrocyte-astrocyte phenotype; and third, all the cell types within the O-2A lineage showed enhanced proliferation. This proliferation was not further enhanced by adding PDGF, basic fibroblast growth factor (bFGF), or insulin-like growth factor I (IGF-I) to the defined medium. However, bFGF and IGF-I seemed to influence the fate of O-2A lineage cells in cultures of demyelinated tissue. Basic FGF decreased the percentage of cells expressing galactocerebroside. In contrast, IGF-I increased the relative proportion of oligodendrocytes. Thus, O-2A lineage cells from adult mice display greater phenotypic plasticity and enhanced mitotic potential in response to an episode of demyelination. These properties may be linked to the efficient remyelination achieved in this demyelinating disease. url: https://www.ncbi.nlm.nih.gov/pubmed/2167897/ doi: nan id: cord-288111-0ufc54kw author: ter MEULEN, VOLKER title: Autoimmune Reactions Against Myelin Basic Protein Induced by Corona and Measles Viruses date: 2006-12-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/2462802/ doi: 10.1111/j.1749-6632.1988.tb27062.x ==== make-pages.sh questions [ERIC WAS HERE] ==== make-pages.sh search /data-disk/reader-compute/reader-cord/bin/make-pages.sh: line 77: /data-disk/reader-compute/reader-cord/tmp/search.htm: No such file or directory Traceback (most recent call last): File "/data-disk/reader-compute/reader-cord/bin/tsv2htm-search.py", line 51, in with open( TEMPLATE, 'r' ) as handle : htm = handle.read() FileNotFoundError: [Errno 2] No such file or directory: '/data-disk/reader-compute/reader-cord/tmp/search.htm' ==== make-pages.sh topic modeling corpus Zipping study carrel