Aminoguanidine, an inhibitor of inducible nitric oxide synthase, ameliorates experimental autoimmune encephalomyelitis in SJL mice

Anne H. Cross, Thomas P. Misko, Robin F. Lin, William F. Hickey, John L. Trotter, Ronald G. Tilton

Research output: Contribution to journalArticle

348 Scopus citations

Abstract

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 aminoguanidine, a preferential inhibitor of the inducible nitric oxide synthase isoform, and by N(G)-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.

Original languageEnglish (US)
Pages (from-to)2684-2690
Number of pages7
JournalJournal of Clinical Investigation
Volume93
Issue number6
DOIs
StatePublished - Jun 1994

Keywords

  • allergic encephalomyelitis
  • autoimmune diseases
  • demyelinating diseases
  • multiple sclerosis
  • nitric oxide

ASJC Scopus subject areas

  • Medicine(all)

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