Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) result in inflammatory white matter lesions in the CNS. However, information is sparse with regard to the effects of autoimmune demyelinating disease on gray matter regions. Therefore, we studied the late effects of chronic EAE in C57BL/6 mice on the spinal cord gray matter using immunohistochemistry. Here, EAE induced marked astrocytic, microglial, and macrophage activation in the ventral horn gray matter, without any motoneuron loss. Activated caspase-3 was also increased in the ventral horn gray matter. Furthermore, activated poly (ADP-ribose) polymerase (PARP), another apoptotic marker, co-localized with myelin basic protein (MBP) of oligodendrocyte processes, but not with the oligodendroglial cell body marker, adenomatous polyposis coli gene clone CC1 (APC-CC1), or with neurofilament marker (RT-97) or synaptophysin of axonal arbors. However, there was no associated increase in the number of terminal deoxynucleotidyl transferase (TdT) mediated-dUTP nick end labeling positive nuclei in the spinal cord gray matter of EAE mice. In addition, co-localization of MBP and the low-affinity neurotrophin receptor, p75, was demonstrated, further supporting the notion of apoptotic oligodendrocyte process degeneration in the gray matter of EAE mice.
 ...
PMID:Glial reactions and degeneration of myelinated processes in spinal cord gray matter in chronic experimental autoimmune encephalomyelitis. 1871 11

Human Mesenchymal Stem Cells (MSCs) were previously reported to ameliorate neuronal functional deficits in the MOG35-55-induced experimental autoimmune encephalomyelitis (EAE) mice by inducing T cell anergy. Human Ciliary neurotrophic factor (CNTF) recently was found to promote myelogenesis and reduce inflammation in CNTF-deficient EAE mice. We ectopically overexpressed CNTF in human MSCs to investigate its potential role in promoting remyelination and improving functional recovery in EAE mice. MSCs transfected by Ad-CNTF-IRES-EGFP (MSC-CNTF) were injected intravenously into EAE mice 10 days after the immunization. Neurological functional tests were scored daily by grading clinical signs (score 0-6). Immunofluorescence microscopy was used to detect MSC-CNTF in spinal cord. Expression of NG2, CNTF, and cleaved caspase-3 was measured by immunohistochemistry. CNTF expression was also analyzed by Western blot. Myelin was detected by Solochrome Cyanin staining. Our results found that CNTF concentration in MSC-CNTF cells was 20-fold higher than that in either MSC or Ad-EGFP-transfected MSCs (MSC-EGFP) in vitro. Mice receiving MSC-CNTF cells showed remarkable neuronal functional recovery: the cumulative clinical scores were significantly decreased, and the disease onset was statistically delayed. Mice receiving MSC-CNTF cells showed reduced TNF-alpha, IFN-gamma and increased the level of cytokine IL-10 in peripheral blood and a large number of MSC-CNTF cells were detected in the spleen, but were not detected in other organs such as lung, liver and kidney. In the lesions of these mice, 1) the number of cleaved caspase3-positive cells was significantly reduced; 2) MSC-CNTF- and NG2-positive cells were significantly increased; and 3) the expression of CNTF was dramatically increased. In addition, demyelination was significantly reduced in MSC-CNTF mice. These data indicated that MSC-CNTF may improve functional recovery in EAE mice, possibly by exerting their immunoregulatory activity, inhibiting inflammation, homing MSC-CNTF cells to the lesions, elevating CNTF expression, reducing demyelination, and stimulating oligodendrogenesis.
 ...
PMID:Overexpression of CNTF in Mesenchymal Stem Cells reduces demyelination and induces clinical recovery in experimental autoimmune encephalomyelitis mice. 1908 Nov 44

Alpha-fetoprotein (AFP) is an immunomodulatory glycoprotein associated with the normal growth of the mammalian fetus. Ws have shown that treatment with recombinant human AFP (rhAFP) reduced lymphocyte reactivity and the extent of neuroinflammation in mice with experimental autoimmune encephalomyelitis (EAE). In the present study we found involvement of AFP in immune cell apoptosis, attesting to its possible mechanism of action. AFP increased the expression of the Bax, Bid, Bad and ApaF genes in peripheral lymphocytes, together with an enhanced expression of Caspase-3, Fas, FasL and TRAIL among infiltrating immune cells. The induction of apoptosis markers was accompanied with an increased expression of Foxp3 in lymph node cells, as well as accumulation of CD4+Foxp3+ regulatory T cells in the CNS. Overall, these immunological alterations gave rise to a milder disease and accelerated remission rate. Our results suggest a new role for AFP in controlling the autoimmune inflammation associated with EAE.
 ...
PMID:Immunomodulation of EAE by alpha-fetoprotein involves elevation of immune cell apoptosis markers and the transcription factor FoxP3. 1917 55

We describe the generation of a fusion cytokine consisting of GM-CSF in tandem with N-terminal-truncated MCP-1 (6-76), hereafter GMME1. Treatment of activated T cells with recombinant GMME1 protein leads to proinflammatory cytokine reduction and apoptosis via a CCR2-restricted pathway. Similarly, cell death is triggered in macrophages cultured with GMME1, while an inhibition of Ab production from plasma cells is observed. Treatment of CD4 T cells derived from experimental autoimmune encephalomyelitis mice with GMME1 leads to p38 hyperphosphorylation, inhibition of p44/42, AKT and STAT3 phosphorylation, and caspase-3 activation. GMME1 administration to experimental autoimmune encephalomyelitis mice suppresses symptomatic disease and correlates with decreased levels of inflammatory cytokines including IL-17, MOG-specific Ab titers, and blockade of CD4 and CD8 T cell infiltration in spinal cords. We propose that GMME1 defines a new class of agents for the treatment of autoimmune ailments by selectively targeting lymphomyeloid cells expressing CCR2.
 ...
PMID:Selective inhibition of CCR2 expressing lymphomyeloid cells in experimental autoimmune encephalomyelitis by a GM-CSF-MCP1 fusokine. 1923 56

Gray matter atrophy observed by brain MRI is an important correlate to clinical disability and disease duration in multiple sclerosis. The objective of this study was to link brain atrophy visualized by neuroimaging to its underlying neuropathology using the MS model, experimental autoimmune encephalomyelitis (EAE). Volumetric changes in brains of EAE mice, as well as matched healthy normal controls, were quantified by collecting post-mortem high-resolution T2-weighted magnetic resonance microscopy and actively stained magnetic resonance histology images. Anatomical delineations demonstrated a significant decrease in the volume of the whole cerebellum, cerebellar cortex, and molecular layer of the cerebellar cortex in EAE as compared to normal controls. The pro-apoptotic marker caspase-3 was detected in Purkinje cells and a significant decrease in Purkinje cell number was found in EAE. Cross modality and temporal correlations revealed a significant association between Purkinje cell loss on neuropathology and atrophy of the molecular layer of the cerebellar cortex by neuroimaging. These results demonstrate the power of using combined population atlasing and neuropathology approaches to discern novel insights underlying gray matter atrophy in animal models of neurodegenerative disease.
 ...
PMID:Purkinje cell loss in experimental autoimmune encephalomyelitis. 1958 88

Many viruses, including picornaviruses, have the potential to infect the central nervous system (CNS) and stimulate a neuroinflammatory immune response, especially in infants and young children. Cognitive deficits associated with CNS picornavirus infection result from injury and death of neurons that may occur due to direct viral infection or during the immune responses to virus in the brain. Previous studies have concluded that apoptosis of hippocampal neurons during picornavirus infection is a cell-autonomous event triggered by direct neuronal infection. However, these studies assessed neuron death at time points late in infection and during infections that lead to either death of the host or persistent viral infection. In contrast, many neurovirulent picornavirus infections are acute and transient, with rapid clearance of virus from the host. We provide evidence of hippocampal pathology in mice acutely infected with the Theiler's murine encephalomyelitis picornavirus. We found that CA1 pyramidal neurons exhibited several hallmarks of apoptotic death, including caspase-3 activation, DNA fragmentation, and chromatin condensation within 72 hours of infection. Critically, we also found that many of the CA1 pyramidal neurons undergoing apoptosis were not infected with virus, indicating that neuronal cell death during acute picornavirus infection of the CNS occurs in a non-cell-autonomous manner. These observations suggest that therapeutic strategies other than antiviral interventions may be useful for neuroprotection during acute CNS picornavirus infection.
 ...
PMID:Apoptosis of hippocampal pyramidal neurons is virus independent in a mouse model of acute neurovirulent picornavirus infection. 1960 74

Oligodendroglial cell death is a frequent phenomenon of many neurological diseases, e.g. in demyelinating diseases such as multiple sclerosis (MS). The underlying mechanisms are largely unknown. Here, we demonstrate that in the toxic demyelination cuprizone model, oligodendroglial cell death and downregulation of myelin genes start days after initiation of the cuprizone diet and weeks before demyelination is obvious. In early - but not in later - stages, dying oligodendrocytes express activated caspase 3, suggesting a switch from classical apoptotic pathways to caspase 3-independent mechanisms during the course of the cuprizone diet. The expression level of FAS in the corpus callosum, a cell death receptor crucial for oligodendroglial cell death in experimental autoimmune encephalomyelitis (EAE), correlates with the expression of activated caspase 3 in oligodendrocytes. However, mice lacking FAS in oligodendrocytes are not protected against cuprizone-induced oligodendroglial cell death, showing that FAS is dispensable for oligodendroglial cell death in the cuprizone model.
 ...
PMID:In toxic demyelination oligodendroglial cell death occurs early and is FAS independent. 1985 62

Dexamethasone-induced Ras protein 1 (Dexras 1), a brain-enriched member of Ras subfamily of guanosine triphosphatases, as a novel physiologic nitric oxide (NO) effector, anchor neuronal nitric oxide synthase (nNOS) that could form a ternary complex with carboxy-terminal PDZ ligand of nNOS (CAPON) and nNOS, to specific targets to enhance NO signaling. The present study was to explore the expression pattern of Dexras 1 in the development of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. Western blot and immunochemistry analysis showed that the gene and protein expression of Dexras 1 in the central nervous system (CNS) of rats increased significantly during the process of EAE compared with control groups (p < 0.01) and maintain a high level in the remission period. The protein expressions of nNOS and CAPON in hippocampus were approximately paralleled Dexras 1. Immunofluorescence revealed that both neurons and glial cells expressed the Dexras 1 in EAE CNS. Importantly, the damaged CNS in EAE-affected rats showed the codistribution between Dexras 1 and caspase 3, indicating the role of Dexras 1 played in the apoptotic process in EAE. Furthermore, colocalizations of Dexras 1 were observed in neurons and glial cells in CNS with nNOS or CAPON, supporting the ternary complex in this model. Thus, these findings suggest the postulation that Dexras 1 might participate into CNS neuronal cell death and demyelination in the whole process of EAE through regulating the NO signaling by binding to nNOS and CAPON.
 ...
PMID:Spatiotemporal patterns of dexamethasone-induced Ras protein 1 expression in the central nervous system of rats with experimental autoimmune encephalomyelitis. 2008 51

The antiinflammatory and antiapoptotic effects of chondroitin sulfate (CS) are being used to treat osteoarthritis. Recent evidence has revealed that those peripheral effects of CS may also have therapeutic interest in diseases of the central nervous system (CNS). We review here such evidence. Perineuronal nets (PNNs) formed by chondroitin sulfate proteoglycans (CSPGs) may have a neuroprotective action against oxidative stress potentially involved in neurodegeneration. On the other hand, in human neuroblastoma SH-SY5Y cells CS has antioxidant and neuroprotective effects by activating the signaling pathway PKC/PI3K/Akt and inducing the antioxidant enzyme hemoxygenase-1. Consistent with this is the observation that protein kinase C (PKC) blockade overcomes inhibition of neurite outgrowth elicited by CSPGs. In addition, CS protects cortical neurons against excytotoxic death by phosphorylation of intracellular signals and the suppression of caspase-3 activation. Of interest is the finding that a disaccharide derived from CSPG degradation (CSGP-DS) protects neurons against toxicity both in vitro and in vivo. Furthermore, CSGP-DS efficiently protects against neuronal loss in experimental autoimmune encephalomyelitis and uveitis, decreases secretion of tumor necrosis factor-alpha (TNF-alpha) and block necrosis factor kappa B (NF-kappaB) translocation. In conclusion, CS may have neuroprotective properties linked to its antioxidant and antiinflammatory effects.
 ...
PMID:Antioxidant, antiinflammatory and neuroprotective actions of chondroitin sulfate and proteoglycans. 2039 98

Survival of neuronal progenitors (NPCs) is a critical determinant of the regenerative capacity of brain following cellular loss. Herein, we report for the first time, the increased spontaneous apoptosis of the first acute phase of Experimental Autoimmune Encephalomyelitis (EAE) derived neurospheres in vitro. Neuronal as well as oligodendroglial loss occurs during experimental autoimmune encephalomyelitis (EAE). This loss is replenished spontaneously by the concomitant increase in the NPC proliferation evidenced by the presence of thin myelin sheaths in the remodeled lesions. However, remyelination depends upon the survival of NPCs and their lineage specific differentiation. We observed significant increase (P < 0.001) in number of BrdU (+) cells in ependymal subventricular zone (SVZ) in EAE rats. EAE derived NPCs showed remarkable increase in S-phase population which was indeed due to the decrease in G-phase progeny suggesting activation of neuronal progenitor cells (NPCs) from quiescence. However, EAE derived neurospheres showed limited survival in vitro which was mediated by the significantly (P < 0.01) depolarized mitochondria, elevated Caspase-3 (P < 0.001) and fragmentation of nuclear DNA evidenced by single cell gel electrophoresis. Our results suggest EAE induced spontaneous apoptosis of NPCs in vitro which may increase the possibility of early stage cell death in the negative regulation of the proliferative cell number and may explain the failure of regeneration in human multiple sclerosis.
 ...
PMID:Increased spontaneous apoptosis of rat primary neurospheres in vitro after experimental autoimmune encephalomyelitis. 2144 97


<< Previous 1 2 3 4 5 6 Next >>