cord-000725-rafwlw0t	2012	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 ).
cord-001017-4qfhltg4	2013	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 ).
cord-001332-dp6vzgef	2014	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) .
cord-001396-rpnuauwz	2014	
cord-002021-67ao8chx	2016	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.
cord-002119-kl431ev6	2016	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.
cord-002209-xs6qigg4	2016	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
cord-002757-upwe0cpj	2017	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] .
cord-003199-03c9rx3o	2018	
cord-003738-el0wyu74	2019	
cord-004911-fbge8tkc	2001	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 (TCRÏ©), macrophages (CD45 high ) and activation of resident microglia (CD45 low , MHC IIÏ©). 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.
cord-005146-o3roa7br	1989	
cord-005393-rhji4io9	1997	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.
cord-005734-14ba78cz	2003	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.
cord-006824-btcdjmfp	2002	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] .
cord-007170-svsfu7fj	1992	
cord-007603-27m9wz0i	2002	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) .
cord-008523-avkgldnp	2004	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.
cord-008530-yni0poh9	2004	
cord-008586-5jinvuyn	2008	
cord-009577-29u7pdpk	2004	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.
cord-009997-oecpqf1j	2018	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.
cord-010016-fs8pjy1z	2008	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).
cord-010187-ymhcfyxx	2005	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) .
cord-011533-im78xwl8	2020	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.
cord-015352-2d02eq3y	2017	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.
cord-015684-q10sx1dm	2009	
cord-016954-l3b6n7ej	2008	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.
cord-017144-k7fqneup	2005	
cord-017499-51yy7y9n	2008	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) .
cord-017917-7aeh6quc	2005	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)
cord-017954-vobslprh	2016	
cord-017958-18nnwoav	2005	
cord-018034-gx5c9mk8	2006	
cord-018042-qt7055fw	2008	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
cord-020770-wpub7krf	2020	
cord-021069-v9f9874x	2004	
cord-021452-9rukc80y	2009	
cord-021500-sy6lnt7b	2007	
cord-021772-5v4gor2v	2019	
cord-022163-7klzsrpu	2016	
cord-022395-rk31pwoa	2012	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
cord-022594-fx044gcd	2009	
cord-022659-chwk2bs4	2004	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).
cord-022756-kdgo4rqb	2012	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.
cord-023026-2r84ndzv	2013	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.
cord-023143-fcno330z	2004	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.
cord-026031-hnf5vayd	2009	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
cord-028963-u4iupl1s	2020	
cord-030371-wp6xmaqe	2019	
cord-104265-kcygxo7h	2000	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 Ï© 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) .
cord-252389-xrdbmosj	2020	
cord-252569-9rv1p3qh	2019	
cord-253201-r6vsa0pw	2020	
cord-253797-a9lmfaho	1993	
cord-257167-rz4r5sj7	2006	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).
cord-259347-3acsko74	2020	
cord-262281-56tbrl8a	2007	
cord-262786-otxpc46a	2020	
cord-264794-bgygebgx	1992	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).
cord-266078-h53zpjab	2019	
cord-266441-sd117tzs	2020	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.
cord-267166-ecmayzr6	2018	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.
cord-268341-103xf3dw	1997	
cord-268835-catuja6c	2007	
cord-269861-r07osd0w	2016	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.
cord-270084-xs0pbcip	1988	
cord-270458-7imgvale	2020	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.
cord-270780-3g381rzr	2004	
cord-271011-5stsx5je	2005	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.
cord-271176-wdc4p4bc	1999	
cord-271396-bol1zpji	2018	
cord-272981-8gahvdt0	1984	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.
cord-274315-08mk8a86	2017	
cord-275795-ee7qyw5h	2018	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.
cord-276533-cxyndepl	1989	
cord-276587-ynionj5r	2018	
cord-277679-sc9hugxr	2020	
cord-278684-txlvla0j	1998	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
cord-280987-uhxk5b1b	2014	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.
cord-283850-kt8n6pg2	2020	
cord-284038-93s3ffoy	2020	
cord-285493-eg2ltip6	2007	
cord-288111-0ufc54kw	2006	
cord-290566-tmsocyfc	2007	
cord-292255-zafnq8gl	2016	
cord-294812-nnlzwaf1	2014	
cord-295041-5vpawtef	2020	
cord-297325-fbilhauu	2015	
cord-297448-aiorjsyh	2019	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) .
cord-298847-szezd2vb	2003	
cord-299051-5r2s8z1a	2010	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] .
cord-299949-kmn53e2z	2016	
cord-299967-90aknp7c	2012	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.
cord-302796-zi3p2k1b	2008	
cord-303741-1ou0cy5k	2020	
cord-304084-ervaxqph	2006	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 Ï­ 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 Ï­ 0.005 with Kruskal-Wallis test). EV71 cases with pulmonary edema had a significantly lower PHA stimulation index (p Ï­ 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).
cord-308201-lavcsqov	2019	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.
cord-309109-c5hajb6k	2002	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 .
cord-311845-wnk7itha	2014	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.
cord-311847-2czqs84q	2020	
cord-311908-sgdq6j6x	2000	
cord-312064-hza70mur	1998	
cord-315656-asvf4roo	2020	
cord-316227-dgyxbgvg	2017	
cord-317651-lsca8vt2	2001	
cord-320617-ucm7wx8b	2018	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.
cord-320909-p93gxjm2	2020	
cord-322728-10m3xscs	2016	
cord-324530-tac1unnp	2019	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.
cord-324619-y7gilopu	2020	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.
cord-325624-6anybxnk	2009	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.
cord-328763-hcbs20a0	2020	
cord-329527-0rlotyz3	2018	
cord-329750-purunxce	2006	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] .
cord-330553-sukrjl22	2020	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
cord-331268-kzy33hdb	1996	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) .
cord-332109-ont0tqpn	2020	
cord-333186-gxs74wit	2014	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.
cord-334499-fz7vrnb1	2007	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.
cord-334577-wb6zhovi	2020	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.
cord-337365-hugenn14	2019	
cord-338235-vz2d2x18	2010	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.
cord-340008-2efzyki4	2020	
cord-342204-9tgxijvn	2020	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
cord-345254-glm2dxhh	2015	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.
cord-345339-kyboibtq	2001	
cord-346339-y7z1sa8y	2016	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.
cord-348746-yaf61cmx	2008	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 CD8Ï© 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
cord-349135-it5ahzj3	2006	
cord-349285-zmp7sw5q	2014	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.
cord-351398-ftkrd1tj	2006	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.
cord-353242-9vy8k6du	2020	
cord-353298-vr5hnzp8	1990	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) .
cord-353812-4oxbczqe	2020	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.
cord-355413-ls2nud43	2010	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.