The role of nitric oxide in the pathogenesis of multiple sclerosis

We examined the expression and roles of neuroprotective metallothionein‐I+II (MT‐I+II) in the rat CNS in experimental autoimmune encephalomyelitis (EAE), an animal model for the human autoimmune disease, multiple sclerosis (MS). EAE caused significant macrophage activation, T‐lymphocyte infiltration, and astrogliosis in spinal cord, brain stem, and cerebellum, which peaked 14–18 days after immunization. The remission of symptoms and histopathological changes began at days 19–21 and were completed by days 30–40. MT‐I+II expression was increased significantly in EAE infiltrates. In order to study the effects of increased MT levels, we administered Zn‐MT‐II intraperitoneally (i.p.) to rats during EAE. Clinically, Zn‐MT‐II treatment reduced the severity of EAE symptoms and mortality in a time‐ and dose‐dependent manner. Histopathologically, Zn‐MT‐II increased reactive astrogliosis and decreased macrophages and T lymphocytes significantly in the CNS. In spleen sections, the number of macrophages both in control and EAE‐sensitized rats was reduced by Zn‐MT‐II, while the number of lymphocytes remained unaltered by Zn‐MT‐II. Therefore, we suggest that MT‐II has peripheral mechanisms of action on macrophages, while T lymphocytes are affected locally in the CNS. During EAE, oxidative stress was decreased by Zn‐MT‐II, which could contribute to the diminished clinical scores observed. None of the effects caused by Zn‐MT‐II could be attributable to the zinc content. These results suggest MT‐I+II as potentially useful factors for the treatment of EAE/MS. GLIA 32:247–263, 2000. © 2000 Wiley‐Liss, Inc.

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Neuroprotective Role of Aminoguanidine in Behavioral Changes after Blast Injury

Moochhala

Shirhan

et al. 2004

The Journal of Trauma: Injury, Infection, and Critical Care

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The role of nitric oxide in the pathogenesis of multiple sclerosis

Cited by 4 publications

References 76 publications

Expression of nitric oxide synthase-2 (NOS-2) in reactive astrocytes of the human glaucomatous optic nerve head

Expression of nitric oxide synthase-2 (NOS-2) in reactive astrocytes of the human glaucomatous optic nerve head

Metallothionein I+II expression and their role in experimental autoimmune encephalomyelitis

Neuroprotective Role of Aminoguanidine in Behavioral Changes after Blast Injury

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