UMLS:C0014070 - FACTA Search

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Query: UMLS:C0014070 (encephalomyelitis)
13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously used antibodies to the NG2 proteoglycan and the alpha receptor for platelet-derived growth factor (PDGF alpha receptor) to identify oligodendroglial progenitor cells in vivo and in vitro. It has recently become evident that the GD3 antigen, which has been widely used as a marker for oligodendrocyte progenitor cells, is also expressed by microglial cells. In this study we have examined the relationship between the NG2+/PDGF alpha receptor+ glial progenitor cells and microglial cells in normal developing and mature rat brain and in inflammatory lesions in mice with experimental autoimmune encephalomyelitis (EAE). Double-labeling of sections from normal rat brain using anti-NG2 antibodies and lectin from Griffonia simplicifolia (GSA I-B4) or monoclonal antibody 4H1 indicated that there is no overlap between NG2+ glial progenitor cells and microglia in the parenchyma of the central nervous system. In EAE lesions, both NG2+ cells and microglia, identified by antibodies to F4/80 and CD45, displayed reactive changes characterized by increased cell number and staining intensity and shortening and thickening of cell processes. Both cell types were found surrounding perivascular infiltrates of lymphocytes. Double-labeling EAE sections for NG2 and F4/80 or CD45 failed to reveal cells that co-expressed both antigens, suggesting that reactive NG2+ cells are distinct from activated microglia. However, a close spatial relationship between NG2+ cells and microglia was observed in the normal brain and to a greater extent in EAE, where processes of an activated microglial cell were sometimes seen to encircle an NG2+ cell. These observations are indicative of a functional interaction between microglia and the NG2+ glial cells.
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PMID:Normal and reactive NG2+ glial cells are distinct from resting and activated microglia. 916 56

Remyelination is an extremely efficient process in the adult rodent central nervous system yet the source of new oligodendroglia that appear following primary demyelination is still subject to much debate. Using a reliable marker for oligodendroglial progenitor cells in vivo, the NG2 chondroitin sulphate proteoglycan, we have evaluated the response of endogenous NG2(+) cells in the adult rat brain stem and cerebellum to inflammatory demyelinating lesions in an experimentally induced animal model of multiple sclerosis (MS), antibody augmented experimental allergic encephalomyelitis (ADEAE). We have manipulated T-cell mediated EAE in Lewis rats by injecting in addition, either anti-myelin/oligodendroglial glycoprotein (MOG) antibodies to induce inflammatory demyelination, or non-specific mouse immunoglobulins to induce an inflammatory response without demyelination. We have examined the relationship of NG2(+) progenitor cells to microglia (OX-42(+)), astrocytes (GFAP(+)) and mature oligodendroglia (CNP(+)), in the normal and demyelinated CNS. In the normal CNS NG2-expressing cells are closely intermingled with other glia but represent a distinct cell population. A prominent inflammatory response, identified by the presence of large perivascular and periventricular accumulations of reactive OX42(+) macrophages/microglia, occurred in animals with ADEAE at 7-9 days post injection (DPI), coinciding with severe clinical symptoms. In animals injected with anti-MOG antibodies inflammation was followed by the appearance of large areas of demyelination at 11-14 DPI, at which point the animals had recovered clinically. The response of NG2(+) cells was different depending on whether the inflammation was accompanied by demyelination. In the presence of inflammation, NG2(+) cells responded by an increase in immunoreactivity and an alteration in their morphology, exhibiting enlarged cell bodies and an increased number of intensely stained processes. In areas of demyelination NG2(+) cells had fewer intensely stained processes reminiscent of progenitor cells seen during development. Quantitative analysis revealed a 3-fold increase in the number of NG2(+) cells in demyelinated lesions at 11 DPI, whereas no change was observed in areas of inflammation in the absence of demyelination. Mitotic figures were only seen in NG2(+) cells in areas of demyelination. NG2(+) cell numbers appeared to return to control levels following remyelination. These results suggest that endogenous oligodendroglial progenitors divide and/or migrate, in response to signals triggered by demyelinating rather than inflammatory events, to generate a large progenitor population sufficient to promote the rapid and successful remyelination observed in this model.
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PMID:Generation of oligodendroglial progenitors in acute inflammatory demyelinating lesions of the rat brain stem is associated with demyelination rather than inflammation. 1073 77

Transplanted neural precursor cells remyelinate efficiently acutely demyelinated focal lesions. However, the clinical value of cell transplantation in a chronic, multifocal disease like multiple sclerosis will depend on the ability of transplanted cells to migrate to the multiple disease foci in the brain. Here, we expanded newborn rat neural precursor cells in spheres and transplanted them intracerebroventricularly or intrathecally in rats. The cells were labeled by the nuclear fluorescent dye Hoechst or by incubation with BrdU to enable their identification at 2 days and 2 weeks after transplantation, respectively. Spheres consisted of PSA-NCAM(+), nestin(+), NG2(-) undifferentiated precursor cells that differentiated in vitro into astrocytes, oligodendrocytes, and neurons. Spheres that were transplanted into intact rats remained mostly in the ventricles or in the spinal subarachnoid space. Following transplantation at peak of experimental autoimmune encephalomyelitis, cells migrated into the brain or spinal cord parenchyma, exclusively into inflamed white matter but not into adjacent gray matter regions. After 2 weeks, many transplanted cells had migrated into distant white matter tracts and acquired specific markers of the astroglial and oligodendroglial lineages. Thus, the inflammatory process may attract targeted migration of transplanted precursor cells into the brain parenchyma.
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PMID:Transplanted multipotential neural precursor cells migrate into the inflamed white matter in response to experimental autoimmune encephalomyelitis. 1246 47

Using an animal model of endogenous Nerve Growth Factor (NGF) deprivation, we have investigated the effect of this molecule on the distribution of NG2 and CD56-positive cells in the brain of normal and of Experimental Allergic Encephalomyelitis (EAE) rats. We found that the number of these cells is significantly altered in the SubVentricular Zone (SVZ) and in other brain regions. These findings indicate that NGF might be implicated in the regulation of the antigen expressed by oligodendrocyte progenitors (NG2) and of the neural cell adhesion molecule (CD56/NCAM). Both antigens are associated with mechanisms of brain repair thus providing additional evidence for a major role of NGF in the brain response to pathological conditions such as EAE. Acknowledgements.--We thank Prof. R. Levi-Montalcini for her stimulating discussions. We also thank Dr. L. Aloe for critical reading of the manuscript. This study was supported by Proj. Strategico CNR, by AISM and by Fondazione CARISBO, Bologna. Dr. V. Triaca is a recipient of a fellowship from the AISM.
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PMID:Circulating NGF antibody alters the distribution of NG2 and CD56 positive cells in the brain of an animal model of inflammatory disorder. 1282 24

Remyelination of primary demyelinated lesions is a common feature of experimental models of multiple sclerosis (MS) and is also suggested to be the normal response to demyelination during the early stages of MS itself. Many lines of evidence have shown that remyelination is preceded by the division of endogenous oligodendrocyte precursor cells (OPCs) in the lesion and its borders. It is suggested that this rapid response of OPCs to repopulate the lesion site and their subsequent differentiation into new oligodendrocytes is the key to the rapid remyelination. Antibodies to the NG2 chondroitin sulphate proteoglycan have proved exceedingly useful in following and quantitating the response of endogenous OPCs to demyelination. Here we review the literature on the response of NG2-expressing OPCs to demyelination and provide some new evidence on their response to the chronic inflammatory demyelinating environment seen in recombinant myelin oligodendrocyte glycoprotein (MOG) induced experimental allergic encephalomyelitis (EAE) in the DA rat. NG2-expressing OPCs responded to the inflammatory demyelination in this model by becoming reactive and increasing in number in a very focal manner. Evidence of NG2+ OPCs in lesioned areas beginning to express the oligodendrocyte marker CNP was also seen. The response of OPCs appeared to occur following successive relapses but did not always lead to remyelination, with areas of chronic demyelination observed in the spinal cord. The presence of OPCs in the adult human CNS is clearly of vital importance for repair in multiple sclerosis (MS). As in rat tissue, the antibody labels an evenly distributed cell population present in both white and grey matter, distinct from HLA-DR+ microglia. NG2+ cells are sparsely distributed in the centre of chronic MS lesions. These cells apparently survive demyelination and exhibit a multi-processed or bipolar morphology in the very hypocellular environment of the lesion.
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PMID:The response of NG2-expressing oligodendrocyte progenitors to demyelination in MOG-EAE and MS. 1450 Dec 21

We have recently shown that the inflammatory process during experimental allergic encephalomyelitis (EAE), the animal model of MS, attracts transplanted NPC migration into the inflamed white matter. Here we studied how the proinflammatory cytokines tumor necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma) affect NPC growth, survival, differentiation, and migration. Newborn rat striatal NPCs were expanded in spheres as nestin+, PSA-NCAM+, NG2(-) cells, which differentiated into astrocytes, oligodendrocytes, and neurons. NPCs expressed receptors of TNFalpha and IFNgamma but not interleukin-1. TNFalpha and IFNgamma inhibited sphere cell proliferation, determined by [(3)H]thymidine and BrdU incorporation. IFNgamma increased apoptotic cell death (determined by TUNEL stains); this effect partially blocked by TNFalpha. Neither cytokine affected NPC lineage fate, determined by percentage of GFAP+, neurofilament+, and GalC+ cells after differentiation. TNFalpha and IFNgamma increased outward migration of cells from spheres in vitro. Thus, TNFalpha and IFNgamma, key players in MS and EAE, inhibit NPC proliferation and induce their migration.
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PMID:Effects of proinflammatory cytokines on the growth, fate, and motility of multipotential neural precursor cells. 1466 13

Erythropoietin (EPO), originally recognized for its central role in erythropoiesis, has been shown to improve neurological outcome after stroke. Here, we investigated the treatment of experimental autoimmune encephalomyelitis (EAE) in mice with EPO. Mice were treated with recombinant human EPO (rhEPO) upon onset of paresis. Neurological functional tests were scored daily by grading of clinical signs (score 0-5). Hematoxylin and eosin (HE) staining of cerebral tissue was performed to detect inflammatory infiltrates. Double staining for Luxol fast blue and Bielshowsky was used to demonstrate myelin and axons, respectively. Immunohistochemistry was performed to measure the expression of bromodeoxyuridine (BrdU, a marker for cell proliferation), NG2 (a marker for oligodendrocyte progenitor cells) and brain-derived neurotrophic factor (BDNF). Treatment with rhEPO significantly improved neurological functional recovery, reduced inflammatory infiltrates and demyelination, and increased oligodendrocyte progenitor cell proliferation and BDNF+ cells compared to the EAE controls. These data indicate that rhEPO treatment improved functional recovery after EAE in mice, possibly, via stimulating oligodendrogenesis, downregulating proinflammatory infiltrates and by elevating BDNF expression.
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PMID:Erythropoietin treatment improves neurological functional recovery in EAE mice. 1571 57

We investigated the treatment of remitting-relapsing experimental autoimmune encephalomyelitis (EAE) in mice with human bone marrow stromal cells (hBMSCs). hBMSCs were injected intravenously into EAE mice upon onset of paresis. Neurological functional tests were scored daily by grading clinical signs (score 0-5). Immunohistochemistry was performed to measure the transplanted hBMSCs, cell proliferation (bromodeoxyuridine, BrdU), oligodendrocyte progenitor cells (NG2), oligodendrocytes (RIP), and brain-derived neurotrophic factor (BDNF). The maximum clinical score and the average clinical scores were significantly decreased in the hBMSC-transplanted mice compared to the phosphate-buffered-saline-treated EAE controls, indicating a significant improvement in function. Demyelination significantly decreased, and BrdU(+) and BDNF(+) cells significantly increased in the hBMSC-treated mice compared to controls. Some BrdU(+) cells were colocalized with NG2(+) and RIP(+) immunostaining. hBMSCs also significantly reduced the numbers of vessels containing inflammatory cell infiltration. These data indicate that hBMSC treatment improved functional recovery after EAE in mice, possibly, via reducing inflammatory infiltrates and demyelination areas, stimulating oligodendrogenesis, and by elevating BDNF expression.
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PMID:Human bone marrow stromal cell treatment improves neurological functional recovery in EAE mice. 1590 21

To determine the possible involvement of protease M/neurosin in demyelinating diseases of the CNS, we examined its expression in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), a recognized animal model of multiple sclerosis (MS). In situ hybridization, immunohistochemistry and quantitative real-time polymerase chain reaction (PCR) demonstrated that EAE caused an increase in the expression of protease M/neurosin mRNA and its protein product throughout the white and gray matter surrounding demyelinating lesions. Combined in situ hybridization and immunohistochemistry demonstrated that most of the cells expressing protease M/neurosin mRNA within control spinal cord showed immunoreactivity for CNPase or NG2, cell-specific markers for oligodendrocytes and their progenitors, respectively. In the spinal cord from mice with EAE, the expression of protease M/neurosin mRNA in CNPase-positive cells appeared to be increased while double-labeled cells positive for protease M/neurosin mRNA and NG2 were rarely found in areas associated with demyelinating lesions. Although a prominent accumulation of inflammatory cells including T-cells was observed in the vicinity of demyelinated lesions, these cells were not associated with protease M/neurosin mRNA expression. The levels of protease M/neurosin mRNA expression were unchanged in the spleen and even decreased in the thymus during the course of EAE. These observations suggest that the differential expression of protease M/neurosin in mature oligodendrocytes and their progenitors is involved in the pathogenesis of MS and EAE.
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PMID:Differential expression of protease M/neurosin in oligodendrocytes and their progenitors in an animal model of multiple sclerosis. 1591 Nov 26

Autoimmune injury to oligodendrocytes evokes an endogenous response in the central nervous system, which initially limits the acute injury to oligodendrocytes and myelin, and subsequently promotes remyelination. The key molecular and cellular events responsible for this beneficial outcome are incompletely understood. In this article, we utilize murine autoimmune encephalomyelitis (EAE) to focus on the effect of endogenously produced leukemia inhibitory factor (LIF) upon mature oligodendrocyte survival after demyelinating injury. We show that the mRNA for LIF is markedly upregulated in the spinal cord in the context of acute inflammatory demyelination. After clinical disease onset, administration of neutralizing anti-LIF antibodies over a four day period significantly worsens disease severity in two different murine EAE models. We also show that administration of neutralizing antibodies results in reduced activation of the cognate LIF receptor components in the spinal cord. Histologically, anti-LIF antibody administration increases the extent of acute demyelination (P < 0.01) and doubles the oligodendrocyte loss already induced by EAE (P < 0.05), without altering the extent of inflammatory infiltration into the spinal cord. Although acute EAE induces a rapid, three-fold increase in the proliferation of NG2 positive oligodendrocyte progenitors (P < 0.001), this response is not diminished by antagonism of endogenous LIF. We conclude that endogenous LIF is induced in response to autoimmune demyelination in the spinal cord and protects mature oligodendrocytes from demyelinating injury and cell death, thereby resulting in attenuation of clinical disease severity.
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PMID:Endogenous leukemia inhibitory factor production limits autoimmune demyelination and oligodendrocyte loss. 1649 19

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