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)

The relationship between axonal degeneration and primary demyelination was studied in isolated rat sciatic nerve fibers previously exposed to antiserum from rabbits with either experimental allergic neuritis or experimental allergic encephalomyelitis, or immunized with antigalactocerebroside antiserum. Continuous demyelination over one to eight or more internodes was seen in association with phagocytic cells or, later, with increased numbers of Schwann cells. Paranodal demyelination was prominent proximal ahd distal to the zone of continuous demyelination. Axonal degeneration affected 5 to 15% of myelinated fibers exposed to antiserum and was not related to the length of demyelination must proximal to the axonal changes. At times, there were seven or eight consecutive demyelinated internodes with no distal axonal degeneration; in contrast, one demyelinated internode was often associated with axonal degeneration beginning just distally. The inflammatory reaction could account for axonal degeneration in antiserum-mediated demyelination.
 ...
PMID:Axonal lesions in acute experimental demyelination: a sequential teased nerve fiber study. 719 32

Experimental allergic encephalomyelitis (EAE) was produced in six adult rhesus monkeys. The animals were evaluated serially by ocular, ophthalmoscopic, fluorescein fundus angiographic, pupillary, visual evoked potential, neurologic, cerebrospinal fluid (CSF), and hematologic examinations and by postmortem detailed histopathologic examination. All the animals developed acute EAE. Four of the monkeys, surviving longer than 1 month, developed chronic relapsing EAE and were sacrificed 3 to 14 months after sensitization. All 12 eyes developed acute optic neuritis (with variable degrees of optic disc edema and visual loss). Later on, all the eyes of animals with chronic EAE developed optic atrophy with total or almost total blindness. Histopathologic examination of the optic nerve and central nervous system revealed inflammatory infiltrates, extensive demyelination, and axonal degeneration, without inflammation in the retina or optic nerve head (i.e., nonmyelinated neural tissue). Relapsing EAE was reflected in episodic increases of CSF proteins and pleocytosis. The various findings are correlated.
 ...
PMID:Experimental allergic encephalomyelitis. I. Optic nerve and central nervous system manifestations. 725 9

The location and distribution of viral RNA were examined in the central nervous system tissues of weanling mice acutely infected with the GDVII strain of Theiler's murine encephalomyelitis virus. Viral RNA was detected by autoradiography following in situ hybridization of a 3H-labeled DNA synthesized in vitro complementary to purified viral RNA. Viral RNA was detected in pyramidal neurons of the hippocampus, cerebral cortex, brainstem nuclei, thalamus, basal ganglia, and spinal cord. Autoradiographic grains could be detected in the axonal and dendritic processes of many infected neurons. No viral RNA was detected in any cell of the cerebellum or white matter. In addition to demonstrating the location of viral RNA in infected central nervous system tissues, and hence the sites of viral replication during this acute polioencephalomyelitis, they indicate that necrosis of hippocampal neurons is due to lytic infection, rather than to hypoxia.
 ...
PMID:Detection of Theiler's virus RNA in mouse central nervous system by in situ hybridization. 732 23

Morphologic analysis of longitudinal sections of lumbar anterior root tissue from rabbits at different stages of chronic experimental allergic encephalomyelitis has revealed new information on Schwann cell behaviour during early remyelination. Some short remyelinated internodes were displaced laterally towards nodes as other internodes elongated in a stepise fashion to occupy the vacated axonal segments. This suggests that a Schwann cell possesses the ability to remodel its myelin sheath after the initial establishment of the internode. Subaxolemmal densification was found to be formed wherever pairs of Schwann cells overlapped and gap junctions were observed between young Schwann cells.
 ...
PMID:Remodelling during remyelination in the peripheral nervous system. 741 13

Previous work from our laboratory localized nitric oxide to the affected spinal cords of mice with experimental autoimmune encephalomyelitis, a prime model for the human disease multiple sclerosis. The present study shows that activated lymphocytes sensitized to the central nervous system encephalitogen, myelin basic protein, can induce nitric oxide production by a murine macrophage cell line. Induction was inhibited by amino-guanidine, a preferential inhibitor of the inducible nitric oxide synthase isoform, and by NG-monomethyl-L-arginine. Aminoguanidine, when administered to mice sensitized to develop experimental autoimmune encephalomyelitis, inhibited disease expression in a dose-related manner. At 400 mg aminoguanidine/kg per day, disease onset was delayed and the mean maximum clinical score was 0.9 +/- 1.2 in aminoguanidine versus 3.9 +/- 0.9 in placebo-treated mice. Histologic scoring of the spinal cords for inflammation, demyelination, and axonal necrosis revealed significantly less pathology in the aminoguanidine-treated group. The present study implicates excessive nitric oxide production in the pathogenesis of murine inflammatory central nervous system demyelination, and perhaps in the human disease multiple sclerosis.
 ...
PMID:Aminoguanidine, an inhibitor of inducible nitric oxide synthase, ameliorates experimental autoimmune encephalomyelitis in SJL mice. 751 95

T cell activation involves not only recognition of antigen presented by the MHC, but also nonspecific interactions termed "costimulation." The costimulatory molecules B7-1 and B7-2 are ligands on antigen-presenting cells for the CD28 and CTLA-4 receptors on T cells. Previously, a fusion protein consisting of human CTLA-4 linked to human Fc was shown to bind B7-1 and B7-2 with high avidity and to prevent specific T cell activation. Here we investigated the effects of a recombinant fusion protein consisting of the extracellular domain of human CTLA-4 bound to mouse IgG2a Fc (CTLA-4-Fc) upon experimental autoimmune encephalomyelitis, a T cell-mediated disease that serves as a model for multiple sclerosis. CTLA-4-Fc prevented experimental autoimmune encephalomyelitis in 26 of 28 CTLA-4-Fc-treated mice (median maximum score 0), whereas 28 of 30 mice treated with control mouse IgG2a developed disease (median maximum score 2.75). Less inflammation and virtually no demyelination or axonal loss occurred in CTLA-4-Fc-treated compared with control-treated mice. Activated splenocytes from CTLA-4-Fc-treated mice were able to transfer disease adoptively to naive recipients. These results indicate a key role for the B7/CD28 system in the development of actively induced murine experimental autoimmune encephalomyelitis, suggesting an area of investigation with therapeutic potential for multiple sclerosis.
 ...
PMID:Long-term inhibition of murine experimental autoimmune encephalomyelitis using CTLA-4-Fc supports a key role for CD28 costimulation. 753 51

The destruction of central nervous system (CNS) myelin, the lipid-rich insulator surrounding axons in the mammalian brain and spinal cord, is the primary pathological finding in multiple sclerosis. Myelin loss can result in a significant clinical deficit, and was originally thought to be permanent, similar to axonal destruction. However, myelin regeneration is now an established phenomenon in both human disease and animal models of CNS demyelination. In this review, the concept of remyelination in demyelinating diseases such as multiple sclerosis is discussed and the usefulness of animal models of CNS demyelination in developing experimental strategies to promote remyelination is examined. Special emphasis is given to the Theiler's murine encephalomyelitis model, which has been the primary animal model used to investigate therapies designed specifically to stimulate myelin repair.
 ...
PMID:Experimental strategies to promote central nervous system remyelination in multiple sclerosis: insights gained from the Theiler's virus model system. 756 22

Susceptible strains of mice infected intracerebrally with Theiler's murine encephalomyelitis virus develop a chronic, progressive, immune-mediated CNS demyelinating disease similar both pathologically and clinically to multiple sclerosis. Previous reports indicated that polyclonal immunoglobulins from mice injected with homogenized spinal cord promote CNS remyelination when given to SJL/J mice chronically infected with Theiler's virus. To explore further both the mechanism(s) and potential therapeutic usefulness of antibodies in the treatment of CNS demyelinating diseases, we made a panel of monoclonal antibodies derived from splenocytes of SJL/J mice injected with homogenized spinal cord, and screened them for their autoantigen-binding capability. Monoclonal IgM autoantibodies from two clones, designated SCH94.03 and SCH94.32, promoted fourfold more CNS remyelination than controls when given to chronically infected SJL/J mice. CNS remyelination, assessed morphologically by the presence of abnormally thin myelin sheaths relative to axonal diameter, correlated with the absence of clinical disease progression. In titration experiments, treatment with SCH94.03 and remyelination had a positive dose-response relationship, and as little as 10 micrograms of antibody promoted remyelination. Both SCH94.03 and SCH94.32 showed multiorgan autoreactivity, and recognized both surface and cytoplasmic determinants on glial cells. We propose that this model provides a unique system to elucidate the mechanism(s) and test the reparative potential of autoantibodies in the treatment of CNS injury.
 ...
PMID:Monoclonal autoantibodies promote central nervous system repair in an animal model of multiple sclerosis. 793 75

The monoclonal antibody (MAb) 5D4 against a keratan sulfate (KS) epitope of bovine cartilage proteoglycan stains ramified microglia in the rat brain. In this study we show that 5D4-positive microglia is abundant in the normal rat spinal cord and nearly absent during both the active and recovery phase of experimental autoimmune encephalomyelitis (EAE) in myelin-immunized Lewis rats. In contrast, during Wallerian degeneration of the optic nerve the density of KS-immunoreactive microglia remains constant. KS immunoreactivity is absent from both normal and transected sciatic nerves, and spinal nerve roots. On immunoblots of spinal cord extracts MAb 5D4 stains a novel type of KS proteoglycans (KSPGs) with an apparent molecular weight mainly between 140 and 200 kd, which significantly decrease in acute EAE. Our data suggest that high levels of KSPG expression correlate to a downregulated immunophenotype of resident macrophages in the nervous system. The lack of detectable KS in peripheral nerve points to a divergent differentiation of bone marrow-derived resident macrophages in the peripheral and central nervous systems and may partially account for the rapid macrophage response to axonal injury in the peripheral nervous system. Downregulation of microglial KSPG could be a prerequisite for a rapid inflammatory response in the central nervous system.
 ...
PMID:Downregulation of microglial keratan sulfate proteoglycans coincident with lymphomonocytic infiltration of the rat central nervous system. 854 28

Multiple sclerosis (MS) is an inflammatory disease of the CNS white matter characterized pathologically by the accumulation of perivascular and parenchymal T lymphocytes (T cells), and macrophage infiltration associated with myelin destruction. MS lesions are also characterized by the death of oligodendrocytes (the myelin-producing cells) and proliferation and hypertrophy of astrocytes with scar tissue (gliosis) replacing normal myelin. These changes result in the loss of axonal conduction for neurons of the CNS and in clinical disability. MS is thought to be an autoimmune disease, in particular because of its analogy with the disease model of experimental allergic encephalomyelitis (EAE). Despite extensive research and the availability of various EAE models in laboratory rodents the etiology of human MS has not been identified, and to date no effective treatment exists. Phylogenetic differences may limit the usefulness of existing EAE models, and indeed no single form of rodent EAE recapitulates all the clinical and pathological features of MS. Here we describe a novel form of EAE created in a nonhuman primate, the common marmoset Callithrix jacchus. Active immunization of these monkeys with whole myelin produces a primary demyelinating disease with a chronic relapsing-remitting course, characterized pathologically by moderate inflammation with prominent and early demyelination and gliosis reminiscent of human MS. Adoptive and passive transfer experiments have permitted definition of the mechanisms responsible for the MS-like pathology. Production of the fully demyelinated lesion requires synergism between encephalitogenic (e.g., disease-inducing) T cells and pathogenic antibody. The antigens of myelin that promote encephalitogenic T cell and antibody responses in this system have been identified. Because of the similarity between the two conditions and the high degree of conservation in immune and nervous system genes between nonhuman primates and humans, future studies of marmoset EAE will likely accelerate the development of therapies for human MS.
 ...
PMID:Creation of a model for multiple sclerosis in Callithrix jacchus marmosets. 910 72


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>