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      Nitric Oxide and TNFα Effects in Experimental Autoimmune Encephalomyelitis Demyelination

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          The involvement of inducible nitric oxide synthase (iNOS), which plays various roles in the progression of autoimmune diseases, was studied in iNOS knockout (KO) mice and wild-type (WT) controls with respect to experimental autoimmune encephalomyelitis (EAE). The iNOS (KO) mice presented a less severe form of the disease than the WT control mice. Although the levels of TNFα decreased in the periphery in both groups, an increase in the number of TNFα-positive cells was detected in the central nervous system during the acute phase of EAE in the WT mice, but not in the KO mice. These findings suggest that NO and TNFα contribute to the pathogenesis of acute EAE.

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          Most cited references 18

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          Nitric oxide: an endogenous modulator of leukocyte adhesion.

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            Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions.

            Multiple sclerosis (MS) brain tissue, spleen, and PBMC were studied using immunocytochemistry and FACS for immunoreactivity for lymphotoxin (LT) and TNF. Both cytokines were identified in acute and chronic active MS lesions but were absent from chronic silent lesions. LT was associated with CD3+ lymphocytes and Leu-M5+ microglia cells at the lesion edge and to a lesser extent, in adjacent white matter. TNF was associated with astrocytes in all areas of the lesion, and with foamy macrophages in the center of the active lesion. In acute lesions, immunoreactivity for TNF in endothelial cells was noted at the lesion edge. No LT or TNF reactivity was detected in Alzheimer's or Parkinson's disease brain tissues but was present at lower levels in central nervous system (CNS) tissue from other inflammatory conditions, except for adrenoleucodystrophy which displayed high levels of LT in microglia. No increase in LT and TNF reactivity was detected in spleen and PBMC of MS patients suggesting specific reactivity within the CNS. These results indicate that LT and TNF may be involved in the immunopathogenesis of MS, and can be detected in both inflammatory cells and cells endogenous to the CNS.
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              Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains.

              The amount of messenger RNA encoding human inducible nitric oxide synthase and the presence and distribution of NADPH diaphorase were determined in tissue sections from multiple sclerosis (MS) and control brains. Levels of human nitric oxide synthase messenger RNA were markedly elevated in MS brains when compared to normal control brains. NADPH diaphorase activity, a histochemical stain reflecting nitric oxide synthase catalytic activity, was detected in reactive astrocytes in active demyelinating MS lesions and at the edge of chronic active demyelinating lesions. Control brains did not contain NADPH diaphorase-positive astrocytes. These results implicate the free radical nitric oxide in the pathogenesis of demyelinating MS lesions.

                Author and article information

                S. Karger AG
                August 2007
                15 August 2007
                : 14
                : 1
                : 32-38
                aNeuroimmunology Unit, Department of Microbiology and Immunology, and bDepartment of Physiology, University of Campinas, Campinas, and cDepartment of Immunology, University of São Paulo, Ribeirão Preto, Brazil
                107286 Neuroimmunomodulation 2007;14:32–38
                © 2007 S. Karger AG, Basel

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                Page count
                Figures: 4, References: 30, Pages: 7
                Original Paper


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