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

Optic nerve and spinal cord tissue from untreated guinea pigs with chronic relapsing experimental autoimmune encephalomyelitis, guinea pigs with experimental autoimmune encephalomyelitis in which the disease was treated with injections of myelin basic protein (MBP) combined with galactocerebroside (GC), and normal guinea pigs, has been studied morphologically, immunocytochemically and morphometrically. MBP/GC treatment induced widespread proliferation of oligodendrocytes and extensive central nervous system (CNS) remyelination in tissue from both sites. Whereas some oligodendrocytes within lesions from treated animals appeared to be derived from surviving cells which underwent mitosis, the frequent occurrence of nests of oligodendrocytes at the periphery of nerve fiber fascicles in optic nerve among perivascular astrocytic elements, raises the possibility that remyelinating oligodendrocytes might possess progenitors located in these regions. Observations from multiple sclerosis lesions showed that oligodendrocyte proliferation and CNS remyelination occur in human subcortical white matter, but to a lesser degree than that seen in the CNS of MBP/GC/treated guinea pigs. Immunocytochemical examination of CNS tissue from experimental autoimmune encephalomyelitis animals confirmed the morphologic identification of oligodendroglia. Preliminary morphometric analysis confirmed the impression of an increase in oligodendroglial cells in MBP/GC-treated animals. This increase was somewhat obscured statistically by a concomitant rise in the number of fibrous astrocytes. In view of the ability of oligodendrocytes to proliferate and produce new myelin in multiple sclerosis, the possibility is raised that an experimental immunologic approach similar to that employed here might have a beneficial effect in the human disease.
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PMID:Induction of oligodendrocyte proliferation and remyelination after chronic demyelination. Relevance to multiple sclerosis. 245 99

Optic nerve tissue from strain 13 guinea pigs sensitized for chronic (relapsing) experimental allergic encephalomyelitis has been examined up to 3 years postinoculation. The changes were compared with the clinical history in each case, with lesions occurring elsewhere in the central nervous system and with optic nerve tissue from a single case of chronic multiple sclerosis. In chronic experimental allergic encephalomyelitis was found that optic neuritis was a consistent finding. Active lesions in the optic nerve were a feature of animals sampled up to 4 months postinoculation. Unlike lesions in the spinal cord, changes occurring in long term animals did not parallel clinical signs. The absence of active lesions in long term animals was apparently not due to a resistance to recurrent disease on the part of the tissue since a second challenge with central nervour system tissue was capable of producing active inflammation in the optic nerve. It appears, therefore, that in its unmanipulated state, chronic experimental allergic encephalomyelitis is more a disease of the spinal cord. Optic nerve changes in the case of multiple sclerosis did not compare well with the guinea pit lesions--discrepancies which we speculate as being related to differences in anatomy, age, species, and longevity of the disease process (among others), rather than a difference in pathogenesis.
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PMID:Optic neuritis and chronic relapsing experimental allergic encephalomyelitis: relationship to clinical course and comparison with multiple sclerosis. 718 1

In experimental allergic encephalomyelitis (EAE), produced by injecting rabbits with whole rabbit spinal cord together with tubercle bacilli and mineral oil, lesions comparable to those seen in the central nervous system are found in the nerve roots, spinal ganglia, and peripheral nerves. When special fractions of bovine white matter are used as antigen in rabbits, the same distribution of lesions is seen but peripheral nerve involvement is relatively less frequent. When rabbit sciatic nerve or spinal ganglia are used as antigen in rabbits, lesions occur only in the roots, ganglia, and peripheral nerves. Lesions are not produced in the central nervous system, nor is there a meningitis. This disease picture has been called experimental allergic neuritis (EAN). The antigenicity of rabbit nerve is not impaired by autoclaving. Sciatic nerve of other mammalian species produces the same disease in rabbits as does rabbit nerve. Optic nerve, used as antigen, produces the typical picture of EAE, not EAN. The optic nerves are not affected in EAN, whereas they commonly contain lesions in EAE. There are differences of symptomatology, referable to the difference in distribution of lesions, between EAE and EAN. The spinal fluid of EAE shows an increase both in the number of cells and in the total protein content. In EAN, the same changes in protein are observed, but usually the cell count remains normal. The cell count appears to be related to the involvement of cerebral and spinal meninges, which is an almost invariable accompaniment of EAE. The skin tests and serologic studies made with homologous and heterologous antigens were essentially non-contributory, apparently as a consequence of the diversity of antigens present in the inoculated materials. The similarity between EAN and certain of the human polyneuritides is indicated and discussed.
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PMID:Allergic neuritis: an experimental disease of rabbits induced by the injection of peripheral nervous tissue and adjuvants. 1324 45

Optic neuritis (ON), inflammation of the optic nerve, is strongly associated with multiple sclerosis. ON pathology is characterized by attack of autoreactive T cells against optic nerve antigens, resulting in demyelination, death of retinal ganglion cells, and cumulative visual impairment. A model of experimental autoimmune encephalomyelitis (EAE) was utilized to study the onset and progression of ON and the neuroprotective efficacy of oral treatment with the calpain inhibitor SNJ 1945. EAE was actively induced in B10.PL mice with myelin basic protein on Days 0 and 2, and mice received twice daily oral dosing of SNJ 1945 from Day 9 until sacrificing (Day 26). Visual function was determined by electroretinogram recordings and daily measurement of optokinetic responses (OKR) to a changing pattern stimulus. Optic nerve and retinal histopathology was investigated by immunohistochemical and luxol fast blue staining. EAE mice manifested losses in OKR thresholds, a measurement of visual acuity, which began early in the disease course. There was a significant bias toward unilateral OKR impairment among EAE-ON eyes. Treatment with SNJ 1945, initiated after the onset of OKR threshold decline, improved visual acuity, pattern electroretinogram amplitudes, and paralysis, with attenuation of retinal ganglion cell death. Furthermore, calpain inhibition spared oligodendrocytes, prevented degradation of axonal neurofilament protein, and attenuated reactive astrocytosis. The trend of early, unilateral visual impairment in EAE-ON parallels the clinical presentation of ON exacerbations associated with multiple sclerosis. Calpain inhibition may represent an ideal candidate therapy for the preservation of vision in clinical ON. As in multiple sclerosis (MS) patients, optic neuritis (ON) and early, primarily monocular loss in spatial acuity is observed in a rodent model (EAE, experimental autoimmune encephalomyelitis). Daily oral treatment with the calpain inhibitor SNJ 1945 preserves visual acuity and preserves retinal ganglion cells (Brn3a, brain-specific homeobox/POU domain protein 3A) and their axons (MOSP, myelin oligodendrocyte-specific protein). Calpain inhibition may represent a candidate therapy for the preservation of vision in ON.
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PMID:Calpain inhibition reduces structural and functional impairment of retinal ganglion cells in experimental optic neuritis. 2751 91

The ability of novel mitochondrial uncoupler prodrug of 2,4-dinitrophenol (DNP), MP201, to prevent neuronal damage and preserve visual function in an experimental autoimmune encephalomyelitis (EAE) model of optic neuritis was evaluated. Optic nerve inflammation, demyelination, and axonal loss are prominent features of optic neuritis, an inflammatory optic neuropathy often associated with the central nervous system demyelinating disease multiple sclerosis. Currently, optic neuritis is frequently treated with high-dose corticosteroids, but treatment fails to prevent permanent neuronal damage and associated vision changes that occur as optic neuritis resolves, thus suggesting that additional therapies are required. MP201 administered orally, once per day, attenuated visual dysfunction, preserved retinal ganglion cells (RGCs), and reduced RGC axonal loss and demyelination in the optic nerves of EAE mice, with limited effects on inflammation. The prominent mild mitochondrial uncoupling properties of MP201, with slow elimination of DNP, may contribute to the neuroprotective effect by modulating the entire mitochondria's physiology directly. Results suggest that MP201 is a potential novel treatment for optic neuritis.
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PMID:Mitochondrial Uncoupler Prodrug of 2,4-Dinitrophenol, MP201, Prevents Neuronal Damage and Preserves Vision in Experimental Optic Neuritis. 2868 May 31

Changes in gene expression that occur across the central nervous system (CNS) during neurological diseases do not address the heterogeneity of cell types from one CNS region to another and are complicated by alterations in cellular composition during disease. Multiple sclerosis (MS) is multifocal by definition. Here, a cell-specific and region-specific transcriptomics approach was used to determine gene expression changes in astrocytes in the most widely used MS model, experimental autoimmune encephalomyelitis (EAE). Astrocyte-specific RNAs from various neuroanatomic regions were attained using RiboTag technology. Sequencing and bioinformatics analyses showed that EAE-induced gene expression changes differed between neuroanatomic regions when comparing astrocytes from spinal cord, cerebellum, cerebral cortex, and hippocampus. The top gene pathways that were changed in astrocytes from spinal cord during chronic EAE involved decreases in expression of cholesterol synthesis genes while immune pathway gene expression in astrocytes was increased. Optic nerve from EAE and optic chiasm from MS also showed decreased cholesterol synthesis gene expression. The potential role of cholesterol synthesized by astrocytes during EAE and MS is discussed. Together, this provides proof-of-concept that a cell-specific and region-specific gene expression approach can provide potential treatment targets in distinct neuroanatomic regions during multifocal neurological diseases.
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PMID:Cell-specific and region-specific transcriptomics in the multiple sclerosis model: Focus on astrocytes. 2927 67