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Encephalomyelitis
Kinds of Encephalomyelitis Terms modified by Encephalomyelitis Selected AbstractsWest Nile Virus Encephalomyelitis in a SheepJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2003Jeff W. Tyler No abstract is available for this article. [source] An under-active or over-active internal world?THE JOURNAL OF ANALYTICAL PSYCHOLOGY, Issue 2 2005An exploration of parallel dynamics within psyche, Myalgic Encephalomyelitis, in patients with Chronic Fatigue Syndrome, the difficulty of internal regulation Abstract:, This paper explores the dynamics brought into analytic work when there is a symmetric fusion between psyche and soma within the patient. It will consider how such a fusion may emerge from reverberations between physical constitution and a lack of maternal attunement, containment and reflective function. I will describe the work with a patient, Jane, who was diagnosed with Myalgic Encephalomyelitis (ME) during the course of her analysis. The dynamic of her physical symptoms within the analytic work, and the impact of her internal affects and internal ,objects' within the transference and countertransference, indicated a difficulty in finding an homeostatic balance resulting in overactivity and underactivity at both somatic and psychological levels. Using the clinical work with Jane this paper will also examine the interrelationship between mother-infant attachment, an inadequate internalized maternal reflective function, affect dysregulation, unconscious fusion, the lack of psyche-soma differentiation and the impact of the latter in relation to internal regulation systems, or lack of, in patients with Chronic Fatigue Syndrome (CFS) and Myalgic Encephalomyelitis (ME). I will draw on similar work carried out by Holland (1997), Simpson (1997) and Simpson et al. (1997). The paper will also employ the concept of the reflective function (Fonagy 2001; Knox 2003), and consider Matte-Blanco's (1999) concepts of generalization and unconscious symmetry in relation to the patient's internal world. I go on to consider how analysis provides a point outside the ,fusion' that can enable the ,deadlock' to be broken. [source] How to successfully apply animal studies in experimental allergic encephalomyelitis to research on multiple sclerosisANNALS OF NEUROLOGY, Issue 1 2006Lawrence Steinman MD In their Point of View entitled "Experimental Allergic Encephalomyelitis: A Misleading Model of Multiple Sclerosis," Sriram and Steiner1 wrote, "The most disappointing aspect of EAE [experimental allergic encephalomyelitis] as a potential model for MS is its almost total inability to point toward a meaningful therapy or therapeutic approach for MS." Actually, EAE has led directly to the development of three therapies approved for use in multiple sclerosis (MS): glatiramer acetate, mitoxantrone, and natalizumab. Several new approaches to MS are in clinical trials based on positive indications in preclinical work relying on EAE. New clues to the pathogenesis of MS and new potential surrogate markers for MS are shown from research involving EAE when it is critically coupled with actual findings in MS. There are pitfalls in overreliance on the EAE model, or on any animal model for any human disease. Nevertheless, over the past 73 years, the EAE model has proved itself remarkably useful for aiding research on MS. Ann Neurol 2006;60:12,21 [source] Gene and Protein Expression Profiling of the Microvascular Compartment in Experimental Autoimmune Encephalomyelitis in C57BI/6 and SJL MiceBRAIN PATHOLOGY, Issue 1 2005Carsten Alt Dysfunction of the blood-brain barrier (BBB) is a hallmark of inflammatory diseases of the central nervous system (CNS) such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). The molecular mechanisms leading to BBB breakdown are not well understood. In order to find molecules involved in this process, we used oligonucleotide microarrays and proteomics to analyze gene and protein expression of the microvascular compartment isolated from brains of C57BI/6 and SJL/N mice afflicted with EAE and the microvascular compartment isolated from healthy controls. Out of the 6500 known genes and expressed sequence tags (ESTs) studied, expression of 288 genes was found to be changed. Of these genes 128 were altered in the microvascular compartment in both EAE models. Six proteins were identified to be present at altered levels. In addition to the expected increased expression of genes coding for molecules involved in leukocyte recruitment, genes not yet ascribed to EAE pathogenesis were identified. Thus, proteomics and gene array screens of the microvascular compartment are valid approaches, that can be used to define novel candidate molecules involved in EAE pathogenesis at the level of the BBB. [source] Upregulation of Group 1 CD1 Antigen Presenting Molecules in Guinea Pigs with Experimental Autoimmune Encephalomyelitis: An Immunohistochemical StudyBRAIN PATHOLOGY, Issue 1 2003Barbara Cipriani In humans, group 1 CD1 glycoproteins present foreign and self lipid and glycolipid antigens to Tcells. Homologues of these molecules are not found in mice or rats but are present in guinea pigs (GPs). We examined CD1 and MHC class II expression in the central nervous system (CNS) of GPs sensitized for experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. In normal GPs and the uninflamed CNS, low-level MHC class II (MHC II) immunoreactivity occurred on vascular elements, meningeal macrophages and parenchymal microglial cells, whereas immunoreactivity for CD1 was absent. In the inflamed CNS, the majority of infiltrating cells were MHC II+ and microglia showed increased expression. CD1 immunoreactivity was detected on astrocytes and subsets of inflammatory cells including B cells and macrophages. Minimal CD1 and MHC II co-expression was noted on inflammatory cells or glia. We conclude that group 1 CD1 molecules are strongly upregulated in the inflamed CNS on subsets of cells distinct from the majority of MHC II bearing cells. The expression of CD1 proteins in such lesions broadens the potential repertoire of antigens recognized at these sites and highlights the value of the GP as a model for studies of the relevance of CD1 molecules in host defense and autoimmune diseases. [source] MHC Gene Related Effects on Microglia and Macrophages in Experimental Autoimmune Encephalomyelitis Determine the Extent of Axonal InjuryBRAIN PATHOLOGY, Issue 3 2002Maria K. Storch Myelin-oligodendrocyte-glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in rats is a chronic inflammatory demyelinating disease of the central nervous system (CNS) strongly mimicking multiple sclerosis (MS). We determined the involvement of macrophages and microglia in the lesions of MOG-EAE in relation to different major histocompatibility complex (MHC, RT1 in rat) haplotypes. We used intra-RT1 recombinant rat strains with recombinations between the RT1a and RT1u haplotypes on the disease permissive LEW non-MHC genome. Activated microglia and macrophages were identified morphologically and by expression of ED1 and allograft inhibitory factor-1 (AIF-1), and differentiated by their morphological phenotype. White matter lesions contained more macrophages and less microglia compared to grey matter lesions. Similarly active lesions were mainly infiltrated by macrophages, while microglia were abundant in inactive demyelinated plaques. In addition, we found a highly significant genetic association between a macrophage or microglia dominated lesional phenotype, which was independent from location and activity of the lesions. This was not only the case in demyelinating plaques of chronic EAE, but also in purely inflammatory lesions of acute passive transfer EAE. Rat strains with an u-haplotype in both the Class II and the telomeric non-classical Class I region revealed inflammatory and demyelinating lesions, which were dominated by activated microglia. The a-haplotype in any of these regions was associated with macrophage dominated lesions. A comparison of lesions, exactly matched for stages of demyelinating activity in these different rat strains, showed that in spite of a similar extent of demyelination, axonal injury was significantly less in microglia compared to macrophage dominated lesions. Thus, our studies document a genetic influence of the MHC-region on the relative contribution of macrophages versus microglia in the pathogenesis of EAE. [source] Diagnosing paediatric multiple sclerosis versus acute disseminated encephalomyelitisDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 12 2007Daniela Pohl No abstract is available for this article. [source] Gliomatosis cerebri in a 10,year-old girl masquerading as diffuse encephalomyelitis and spinal cord tumourDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 2 2001Sandeep Jayawant Gliomatosis cerebri is the unifying term used when diffuse glial infiltration occurs throughout the cerebral hemispheres. The very few cases reported in children have presented with intractable epilepsy, corticospinal tract deficits, unilateral tremor, headaches, and developmental delay. Antemortem diagnosis is difficult because of the vagueness of the physical, radiological and pathological findings. Adult cases may simulate an acute diffuse encephalomyelitis and show postmortem evidence of a marked swelling of the spinal cord. Apparently benign intracranial hypertension with papilloedema has also been recorded. We report a 10,year-old girl who presented with a history and physical signs suggestive of benign intracranial hypertension. A diffuse encephalomyelopathy occurred, which was complicated by spinal cord swelling, followed by deterioration and death. Gliomatosis cerebri affecting the brain and spinal cord was found at postmortem examination. [source] L-Selectin-deficient SJL and C57BL/6 mice are not resistant to experimental autoimmune encephalomyelitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2008Chiara Uboldi Abstract L-selectin has been suggested to play a role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Here we demonstrate that L-selectin,/, SJL mice are susceptible to proteolipid protein (PLP)-induced EAE because the compromised antigen-specific T cell proliferation in peripheral lymph nodes is fully compensated by the T cell response raised in their spleen. Transfer of PLP-specific T cells into syngeneic recipients induced EAE independent of the presence or absence of L-selectin on PLP-specific T cells or in the recipient. Leukocyte infiltration into the central nervous system parenchyma was detectable independent of the mode of disease induction and the presence or absence of L-selectin. In addition, we found L-selectin,/, C57BL/6 mice to be susceptible to myelin oligodendrocyte glycoprotein-induced EAE. Taken together, we demonstrate that in SJL and C57BL/6 mice L-selectin is not required for EAE pathogenesis. The apparent discrepancy of our present observation to previous findings, demonstrating a role of L-selectin in EAE pathogenesis in C57BL/6 mice or myelin-basic protein (MBP)-specific TCR-transgenic B10.PL mice, may be attributed to background genes rather than L-selectin and to a unique role of L-selectin in EAE pathogenesis in MBP-TCR-transgenic mice. [source] Activating and inhibitory Fc, receptors can differentially modulate T cell-mediated autoimmunityEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2008Mirentxu Abstract The molecular bases responsible for the loss of T cell tolerance to myelin antigens leading to the onset of multiple sclerosis remain obscure. It has been shown that balanced signaling through activating and inhibitory receptors is critical for the maintenance of tolerance to self antigens in autoimmune disorders. However, although Fc,R have been shown to influence experimental autoimmune encephalomyelitis (EAE) development, their role during pathogenesis remains controversial. Here we have evaluated whether relative expression of activating (Fc,RIII) and inhibitory (Fc,RIIb) Fc,R can modulate myelin-specific T cell response, as well as the susceptibility to develop EAE in mice. While Fc,RIIb,/, mice showed a significant increase in EAE severity, an Fc,RIII deficiency protected mice from disease. In addition, Fc,RIIb,/, mice showed enhanced activation of myelin-specific effector T cells, which were significantly more effective at causing EAE in adoptive transfer experiments than were T cells from wild-type mice. In contrast, Fc,RIII,/, mice showed a significantly reduced activation of myelin-specific T cells and these cells failed to adoptively transfer EAE. Consistently, increased expansion of regulatory T cells (Treg) during EAE was observed only for Fc,RIII,/, mice, which were able to suppress disease when adoptively transferred to recipient mice. These findings suggest that the balance between activating and inhibitory Fc,R signaling can contribute to the maintenance of T cell tolerance to myelin antigens and modulate EAE progression. [source] Malondialdehyde modification of myelin oligodendrocyte glycoprotein leads to increased immunogenicity and encephalitogenicityEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2007Maja Wållberg Abstract Self proteins may become autoantigenic through structural modification. We studied malondialdehydation of recombinant rat (rr) myelin oligodendrocyte glycoprotein (MOG), an autoantigen in multiple sclerosis. Malondialdehyde (MDA) modification changed protein weight and charge, the location of these adducts being mapped by Fourier transform ion cyclotron resonance. Molecular modelling revealed significant differences in the MDA-rrMOG three-dimensional structure. DBA/1 mice immunised with MDA-rrMOG developed greater proliferative responses and more severe experimental autoimmune encephalomyelitis than mice immunised with unmodified rrMOG. MDA-rrMOG was taken up more effectively by antigen-presenting cells (APC), at least partially through scavenger receptors. Exposure to MDA-rrMOG led to increased expression of IL-23, IL-12 and IL-12R, indicating a role not only for increased antigen uptake but also for activation of APC. We thus provide biochemical, structural, immunological and clinical data that suggest that the post-translationally modified form of this myelin autoantigen is a more relevant form of the molecule. [source] The role of the ICOS/B7RP-1 T cell costimulatory pathway in murine experimental autoimmune uveoretinitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2006Yoshihiko Usui Abstract ICOS/B7RP-1 is a new member of the CD28/B7 family of costimulatory molecules and plays differential roles in autoimmune diseases. In this study, we examined the role of ICOS/B7RP-1 pathway in the pathogenesis of mouse experimental autoimmune uveoretinitis (EAU), an animal model of human autoimmune uveitis. ICOS expression was found on infiltrating CD4+ T cells in the region of the retina in EAU-induced mice. The anti-B7RP-1 monoclonal antibody (mAb)-treated or ICOS-deficient mice showed a substantial reduction of disease scores. Blockade of ICOS/B7RP-1 interaction during the effector phase ameliorated the disease, whereas its blockade during the induction phase exhibited no significant effect. Moreover, administration of anti-B7RP-1 mAb effectively ameliorated the disease induced by adoptive transfer of pathogenic T cells. The anti-B7RP-1 mAb treatment inhibited the expansion and/or effector function of pathogenic T cells, given that proliferative response and IFN-, production by lymph node cells were reduced upon restimulation with the antigen peptide in vitro. These results suggest that the ICOS/B7RP-1 interaction plays a critical role in the pathogenesis of uveitis. We also indicated that ICOS-mediated costimulation plays differential roles in EAU and experimental autoimmune encephalomyelitis, which is also a Th1 disease induced in the same manner as EAU. [source] Vasoactive intestinal peptide induces regulatory T cells during experimental autoimmune encephalomyelitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2006Amelia Fernandez-Martin Abstract CD4+CD25+ regulatory T cells (Treg) control the immune response to a variety of antigens, including self-antigens. Several models support the idea of the peripheral generation of CD4+CD25+ Treg from CD4+CD25, T cells. Little is known about the endogenous factors and mechanisms controlling the peripheral expansion of CD4+CD25+ Treg. In this study we report on the capacity of the vasoactive intestinal peptide (VIP), an immunosuppressive neuropeptide, to induce functional Treg in vivo during the development of experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis model. The administration of VIP to EAE mice results in the expansion of the CD4+CD25+, Foxp3-expressing T cells in the periphery and the nervous system, which inhibit encephalitogenic T cell activation. In addition to the increase in the number of CD4+CD25+ Treg, VIP induces more efficient suppressors on a per cell basis. The VIP-generated CD4+CD25+ Treg transfer suppression and significantly ameliorate the progression of the disease. [source] Defining antigen-dependent stages of T cell migration from the blood to the central nervous system parenchymaEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2005Angela Abstract In experimental autoimmune encephalomyelitis (EAE), intravenous transfer of activated CD4+ myelin-specific T cells is sufficient to induce disease. Transferred T cells access the CNS parenchyma by trafficking across the blood brain barrier (BBB) vascular endothelium into the perivascular space, and then across the glial limitans that is made up of astrocytes and microglia. Flow cytometry analysis of cells isolated from CNS tissue does not distinguish between T cell populations at the various stages of migration. In this study, we have used GK1.5 (anti-CD4) treatment along with immunohistochemistry to distinguish between populations of T cells that are associated with the vasculature, T cells that have migrated into the perivascular space, and T cells in the parenchyma. We have also re-evaluated antigen specificity requirements of T cells as they are recruited to the CNS parenchyma. Activated myelin-specific T cells are restricted to the CNS vasculature for at least 24,h post transfer. MHC class II expression on the recipient is required for cells to traffic across the CNS vascular endothelium. Further, Con A-stimulated or non-CNS-specific (ovalbumin-specific) T cells fail to migrate into the perivascular space, and only enter the CNS parenchyma when co-transferred with myelin-specific T cells. Our results indicate that Th1 populations cannot accumulate in the perivascular (subarachnoid, Virchow-Robbins) space without a CNS antigen-specific signal. [source] Specificity, magnitude, and kinetics of MOG-specific CD8+ T,cell responses during experimental autoimmune encephalomyelitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2005Mandy Abstract Experimental autoimmune encephalomyelitis (EAE) has traditionally been thought to be almost exclusively mediated by CD4+ effector T,cells. Here, we provide evidence for the existence of mouse CD8+ T,cells that are specific for an epitope of the myelin oligodendrocyte glycoprotein (MOG). Using a panel of truncated MOG peptides, we have identified the minimal epitope recognized by these T,cells as MOG,37,46. This peptide, while possessing relatively low affinity for H-2Db, efficiently stimulates IFN-, production from MOG-specific CD8+ T,cell lines in vitro and induces EAE in vivo. To further characterize the magnitude and kinetics of expansion of the MOG-specific CD8+ T,cell population in vivo, we used MOG,37,50/H-2Db MHC tetramers to visualize MOG-specific CD8+ effectors in the peripheral lymphoid organs and central nervous system during the course of EAE induction and progression. Our results identify MOG-specific CD8+ T,cells in the central nervous system prior to and after the onset of disease, suggesting that CD8+ T,cells are a possible target for therapeutic intervention during EAE. [source] An MHC anchor-substituted analog of myelin oligodendrocyte glycoprotein,35,55 induces IFN-, and autoantibodies in the absence of experimental autoimmune encephalomyelitis and optic neuritisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2004Mandy Abstract Previous strategies to ameliorate experimental autoimmune encephalitis (EAE) include the treatment of autoreactive T,cells with altered peptide ligands, which contain amino acid substitutions at TCR contact residues. We recently showed that a variant of myelin oligodendrocyte glycoprotein (MOG),35,55 possessing low affinity for MHC (45D) induced anergy in MOG,35,55-specific T,cells and reduced their encephalitogenicity upon adoptive transfer. Here we investigate the characteristics of the primary immune response to this MHC anchor-substituted peptide. Overall, we observed that immunization with 45D resulted in the production of IFN-, and anti-MOG,35,55 autoantibodies at levels similar to those of MOG,35,55-immunized mice with active EAE. However, no symptoms of clinical or histological EAE or overt histological optic neuritis were observed in 45D-immunized mice. Consistent with this finding, 45D-immunized mice did not exhibit CD4+ infiltrates into the CNS. Therefore, MOG,35,55-specific precursors stimulated with a weak ligand (45D) mediate some EAE-associated effector functions but are unable to fully initiate the inflammatory process in the central nervous system that leads to clinical manifestation of EAE. [source] Exacerbation of experimental autoimmune encephalomyelitis in rodents infected with murine gammaherpesvirus-68EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2003James Abstract Viral infections have long been suspected to play a role in the pathogenesis of multiple sclerosis. In the present study, two different rodent models of experimental autoimmune encephalomyelitis (EAE) were used to demonstrate the ability of murine gammaherpesvirus-68 (,HV-68) to exacerbate development of neurological symptoms. SJL mice received UV-inactivated ,HV-68 or intranasal,HV-68, followed by immunization against proteolipid-protein peptide 139,151. Infected mice became moribund within 10,days post-immunization, whereas mice exposed to UV-inactivated ,HV-68 recovered. In the second model, Lewis rats were exposed to UV-inactivated ,HV-68 or to ,HV-68, followed by passive transfer of encephalitogenic T lymphocytes specific for myelin basic protein. Consistently, infected rats had higher clinical scores, and this result was observed during acute or latent ,HV-68 infection. It is unlikely that this ,HV-68-induced exacerbation was due to significant viral replication within the central nervous system since nested PCR, viral plaque assays, and infectious-centers assays demonstrated no detectable virus in spinal cords or brains of infected rodents undergoing EAE. Taken together, these studies demonstrate increased clinical symptoms of EAE in rodents infected by a gammaherpesvirus that has a limited ability to invade the central nervous system. [source] Vaccination with myelin oligodendrocyte glycoprotein adsorbed to alum effectively protects DBA/1 mice from experimental autoimmune encephalomyelitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2003Maja Wållberg Abstract To prevent an organism from developing autoimmunity the body limits the number of autoreactive cells through thymic negative selection and regulates their activity through induction of suppressor T cells. Development of antigen-specific therapies provides an interesting opportunity to imitate the body's own, often effective, method of protection. Our study demonstrates that DBA/1 mice could be protected from experimental autoimmune encephalomyelitis induced through injection of recombinant myelin oligodendrocyte glycoprotein (rMOG) when they were previously immunized intraperitoneally with rMOG adsorbed to aluminium hydroxide. This protection was associated with a decreased IFN-, production by rMOG-specific cells, but not a decreased proliferative response. Protection was long lasting, indicating that MOG-alum vaccination might be developed as a prophylactic therapy in multiple sclerosis. [source] Neurologic manifestations of ulcerative colitisEUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2007R. Scheid Ulcerative colitis (UC) has traditionally been considered to be an inflammatory disease limited to the colonic mucosa. However, since it has been shown that UC is frequently accompanied by various extraintestinal disorders, there is increasing evidence that UC may also manifest in the nervous system. The following review focuses particularly on these possible manifestations of UC, both in the peripheral (PNS), and in the central nervous system (CNS). A systematic literature search according to the MEDLINE database was performed for this purpose. Although a reliable differentiation may clinically not always be possible, three major pathogenic entities can be differentiated: (i) cerebrovascular disease as a consequence of thrombosis and thromboembolism; (ii) systemic and cerebral vasculitis; (iii) probably immune mediated neuropathy and cerebral demyelination. With the exception of thromboembolism and sensorineural hearing loss, evidence for a causal relationship relies merely on single case reports or retrospective case series. Considering the CNS-manifestations, similarities between UC-associated disorders of the white matter and acute disseminated encephalomyelitis (ADEM) are obvious. Epileptic seizures, unspecified encephalopathies and confusional states are most likely epiphenomena that have to be regarded symptomatic rather than as own entities. A prospective study on the neurologic aspects of UC would be very welcome. [source] Mycoplasma pneumoniae -associated myelitis: a comprehensive reviewEUROPEAN JOURNAL OF NEUROLOGY, Issue 2 2006S. Tsiodras Myelitis is one of the most severe central nervous system complications seen in association with Mycoplasma pneumoniae infections and both acute transverse myelitis (ATM) as well as acute disseminated encephalomyelitis (ADEM) have been observed. We reviewed all available literature on cases of Mycoplasma spp. associated ATM as well as ADEM with dominant spinal cord pathology and classified those cases according to the strength of evidence implicating M. pneumoniae as the cause. A wide range of data on diagnosis, epidemiology, immunopathogenesis, clinical picture, laboratory diagnosis, neuroimaging and treatment for this rare entity is presented. The use of highly sensitive and specific molecular diagnostic techniques may assist in clearly elucidating the role of M. pneumoniae in ATM/ADEM syndromes in the near future. Immunomodulating therapies may have a role in treating such cases. [source] Fulminant acute disseminated encephalomyelitis mimicking acute bacterial menigoencephalitisEUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2005A. Harloff Most patients with acute disseminated encephalomyelitis (ADEM) recover quickly under corticosteroid treatment and have a favourable long-term prognosis. We report on a young woman with acute onset of an extensive and solitary white-matter lesion in the left hemisphere. Fever, high pleocytosis and elevated protein in cerebrospinal fluid initially suggested bacterial meningoencephalitis. The patient died from brain herniation despite maximal conservative therapy. Histological changes in necropsy were consistent with the diagnosis ADEM. Treatment options of fulminant ADEM are discussed. [source] Relapsing,remitting demyelinating illness: multiple sclerosis, multiphasic disseminated encephalomyelitis, or an intermediate entity?EUROPEAN JOURNAL OF NEUROLOGY, Issue 2 2002V. I. Bonev No abstract is available for this article. [source] Rapid clinical and CSF response to intravenous gamma globulin in acute disseminated encephalomyelitisEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2001S. J. Pittock [source] CNS-irrelevant T-cells enter the brain, cause blood,brain barrier disruption but no glial pathologyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2007Alina Smorodchenko Abstract Invasion of autoreactive T-cells and alterations of the blood,brain barrier (BBB) represent early pathological manifestations of multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). Non-CNS-specific T-cells are also capable of entering the CNS. However, studies investigating the spatial pattern of BBB alterations as well as the exact localization and neuropathological consequences of transferred non-CNS-specific cells have been thus far lacking. Here, we used magnetic resonance imaging and multiphoton microscopy, as well as histochemical and high-precision unbiased stereological analyses to compare T-cell transmigration, localization, persistence, relation to BBB disruption and subsequent effects on CNS tissue in a model of T-cell transfer of ovalbumin (OVA)- and proteolipid protein (PLP)-specific T-cells. BBB alterations were present in both EAE-mice and mice transferred with OVA-specific T-cells. In the latter case, BBB alterations were less pronounced, but the pattern of initial cell migration into the CNS was similar for both PLP- and OVA-specific cells [mean (SEM), 95 × 103 (7.6 × 103) and 88 × 103 (18 × 103), respectively]. Increased microglial cell density, astrogliosis and demyelination were, however, observed exclusively in the brain of EAE-mice. While mice transferred with non-neural-specific cells showed similar levels of rhodamine-dextran extravasation in susceptible brain regions, EAE-mice presented huge BBB disruption in brainstem and moderate leakage in cerebellum. This suggests that antigen specificity and not the absolute number of infiltrating cells determine the magnitude of BBB disruption and glial pathology. [source] Activation of PPAR-, and PTEN cascade participates in lovastatin-mediated accelerated differentiation of oligodendrocyte progenitor cellsGLIA, Issue 14 2010Ajaib S. Paintlia Abstract Previously, we and others documented that statins including-lovastatin (LOV) promote the differentiation of oligodendrocyte progenitor cells (OPCs) and remyelination in experimental autoimmune encephalomyelitis (EAE), an multiple sclerosis (MS) model. Conversely, some recent studies demonstrated that statins negatively influence oligodendrocyte (OL) differentiation in vitro and remyelination in a cuprizone-CNS demyelinating model. Therefore, herein, we first investigated the cause of impaired differentiation of OLs by statins in vitro settings. Our observations indicated that the depletion of cholesterol was detrimental to LOV treated OPCs under cholesterol/serum-deprived culture conditions similar to that were used in conflicting studies. However, the depletion of geranylgeranyl-pp under normal cholesterol homeostasis conditions enhanced the phenotypic commitment and differentiation of LOV-treated OPCs ascribed to inhibition of RhoA-Rho kinase. Interestingly, this effect of LOV was associated with increased activation and expression of both PPAR-, and PTEN in OPCs as confirmed by various pharmacological and molecular based approaches. Furthermore, PTEN was involved in an inhibition of OPCs proliferation via PI3K-Akt inhibition and induction of cell cycle arrest at G1 phase, but without affecting their cell survival. These effects of LOV on OPCs in vitro were absent in the CNS of normal rats chronically treated with LOV concentrations used in EAE indicating that PPAR-, induction in normal brain may be tightly regulated-providing evidences that statins are therapeutically safe for humans. Collectively, these data provide initial evidence that statin-mediated activation of the PPAR-,-PTEN cascade participates in OL differentiation, thus suggesting new therapeutic-interventions for MS or related CNS-demyelinating diseases. © 2010 Wiley-Liss, Inc. [source] G protein-coupled receptor 84, a microglia-associated protein expressed in neuroinflammatory conditionsGLIA, Issue 8 2007Caroline Bouchard Abstract G protein-coupled receptor 84 (GPR84) is a recently discovered member of the seven transmembrane receptor superfamily whose function and regulation are unknown. Here, we report that in mice suffering from endotoxemia, microglia express GPR84 in a strong and sustained manner. This property is shared by subpopulations of peripheral macrophages and, to a much lesser extent, monocytes. The induction of GPR84 expression by endotoxin is mediated, at least in part, by proinflammatory cytokines, notably tumor necrosis factor (TNF) and interleukin-1 (IL-1), because mice lacking either one or both of these molecules have fewer GPR84-expressing cells in their cerebral cortex than wild-type mice during the early phase of endotoxemia. Moreover, when injected intracerebrally or added to microglial cultures, recombinant TNF stimulates GPR84 expression through a dexamethasone-insensitive mechanism. Finally, we show that microglia produce GPR84 not only during endotoxemia, but also during experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. In conclusion, this study reports the identification of a new sensitive marker of microglial activation, which may play an important regulatory role in neuroimmunological processes, acting downstream to the effects of proinflammatory mediators. © 2007 Wiley-Liss, Inc. [source] Survival of neural precursor cells in growth factor-poor environment: Implications for transplantation in chronic diseaseGLIA, Issue 4 2006Ofira Einstein Abstract A key issue for therapeutic neural stem cell transplantation in chronic diseases is the long-term survival of transplanted cells in the brain. The normal adult central nervous system does not support the survival of transplanted cells. Presumably, the limited availability of trophic factors maintains the survival of resident cells but is insufficient for supporting the survival of transplanted cells. Specifically, in multiple sclerosis, a chronic relapsing disease, it would be necessary to maintain long-term survival of transplanted cells through phases of relapses and remissions. It may be beneficial to transplant cells as early as possible, in a form that will keep their survival independent of tissue support and ready for immediate mobilization upon tissue demand during disease relapse. In the present study, we examined whether, in the form of neurospheres, multipotential neural precursor cells (NPCs) survive in a growth factor-poor environment while maintaining their potential to respond to environmental cues. We found that after removal of growth factors from the culture medium of neurospheres in vitro, NPC proliferation decreased significantly, but most cells survived for a prolonged time and maintained their stem cell characteristics. After re-exposure to growth factors, neurosphere cells resumed proliferation and could differentiate along neural lineages. Furthermore, neurospheres, but not single NPCs, that were transplanted into the brain ventricles of intact animals survived within the ventricles for at least a month and responded to induction of experimental autoimmune encephalomyelitis and brain inflammation by extensive migration into the brain white matter and differentiated into glial lineage cells. © 2005 Wiley-Liss, Inc. [source] Involvement of neuropsin in the pathogenesis of experimental autoimmune encephalomyelitisGLIA, Issue 2 2005Ryuji Terayama Abstract Inflammation, demyelination, and axonal damage of the central nervous system (CNS) are major pathological features of multiple sclerosis (MS). Proteolytic digestion of the blood-brain barrier and myelin protein by serine proteases is known to contribute to the development and progression of MS. Neuropsin, a serine protease, has a role in neuronal plasticity, and its expression has been shown to be upregulated in response to injury to the CNS. To determine the possible involvement of neuropsin in demyelinating diseases of the CNS, we examined its expression in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), a recognized animal model for MS. Neuropsin mRNA expression was induced in the spinal cord white matter of mice with EAE. Combined in situ hybridization and immunohistochemistry demonstrated that most of the cells expressing neuropsin mRNA showed immunoreactivity for CNPase, a cell-specific marker for oligodendrocytes. Mice lacking neuropsin (neuropsin,/,) exhibited an altered EAE progression characterized by delayed onset and progression of clinical symptoms as compared to wild-type mice. Neuropsin,/, mice also showed attenuated demyelination and delayed oligodendroglial death early during the course of EAE. These observations suggest that neuropsin is involved in the pathogenesis of EAE mediated by demyelination and oligodendroglial death. © 2005 Wiley-Liss, Inc. [source] Effect of 1,,25-dihydroxyvitamin D3 in embryonic hippocampal cellsHIPPOCAMPUS, Issue 6 2010Francesca Marini Abstract Although the role of 1,,25-dihydroxyvitamin D3 in calcium homeostasis of bone tissue is clear, evidence of the involvement of vitamin D3 in the central nervous system functions is increasing. In fact, vitamin D3 regulates vitamin D receptor and nerve growth factor expression, modulates brain development, and reverses experimental autoimmune encephalomyelitis. Only few studies, however, address vitamin D3 effect on embryonic hippocampal cell differentiation. In this investigation, the HN9.10e cell line was used as experimental model; these cells, that are a somatic fusion product of hippocampal cells from embryonic day-18 C57BL/6 mice and N18TG2 neuroblastoma cells, show morphological and cytoskeletal features similar to their neuronal precursors. By this model, we have studied the time course of vitamin D3 localization in the nucleus and its effect on proteins involved in proliferation and/or differentiation. We found that the translocation of vitamin D3 from cytoplasm to the nucleus is transient, as the maximal nuclear concentration is reached after 10 h of incubation with 3H-vitamin D3 and decreases to control values by 12 h. The appearance of differentiation markers such as Bcl2, NGF, STAT3, and the decrease of proliferation markers such as cyclin-1 and PCNA are late events. Moreover, physiological concentrations of vitamin D3 delay cell proliferation and induce cell differentiation of embryonic cells characterized by modification of soma lengthening and formation of axons and dendrites. © 2009 Wiley-Liss, Inc. [source] Regulatory T cells and autoimmune diseaseIMMUNOLOGICAL REVIEWS, Issue 1 2005Silke Paust Summary:, Although T-cell clones bearing T-cell receptors with high affinity for self-peptide major histocompatibility complex (MHC) products are generally eliminated in the thymus (recessive tolerance), the peripheral T-cell repertoire remains strongly biased toward self-peptide MHC complexes and includes autoreactive T cells. A search for peripheral T cells that might exert dominant inhibitory effects on autoreactivity has implicated a subpopulation of CD4+CD25+ T cells called regulatory T cells (Tregs). Here, we discuss the role of cytokines and costimulatory molecules in the generation, maintenance, and function of Tregs. We also summarize evidence for the involvement of Tregs in controlling autoimmune diseases, including type 1 diabetes, experimental autoimmune encephalomyelitis, and inflammatory bowel disease. Last, we discuss our recent definition of the potential role of B7 expressed on activated T-effector cells as a target molecule for Treg-dependent suppression. These observations suggest that the engagement of B7 on effector T cells transmits an inhibitory signal that blocks or attenuates effector T-cell function. We restrict our comments to the suppression mediated by cells within the CD4 lineage; the impact of the cells within the CD8 lineage that may suppress via engagement of Qa-1 on effector T cells is not addressed in this review. [source] | ||||||||||||||||||||||||||||||||||||||||