Peroxynitrite formation within the central nervous system in active multiple sclerosis

Anne H. Cross, Pamela T. Manning, Richard M. Keeling, Robert E. Schmidt, Thomas P. Misko

Research output: Contribution to journalArticle

171 Scopus citations

Abstract

Peroxynitrite, generated by the reaction of nitric oxide (NO) with superoxide at sites of inflammation, is a strong oxidant capable of damaging tissues and cells. Detection of nitrotyrosine (NT) at inflammatory sites serves as a biochemical marker for peroxynitrite-mediated damage. In this study, NT was detected immunohistochemically within autopsied CNS tissues from six of nine multiple sclerosis (MS) patients, and in most of the MS sections displaying inflammation. Nitrite and nitrate, the stable oxidation products of NO and peroxynitrite, respectively, were measured in cerebrospinal fluid samples obtained from MS patients and controls. Levels of nitrate were elevated significantly during clinical relapses of MS. These data suggest that peroxynitrite formation is a major consequence of NO produced in MS-affected CNS and implicate a role for this powerful oxidant in the pathogenesis of MS.

Original languageEnglish
Pages (from-to)45-56
Number of pages12
JournalJournal of Neuroimmunology
Volume88
Issue number1-2
DOIs
StatePublished - Aug 1 1998

Keywords

  • Cerebrospinal fluid
  • Demyelination
  • Free radicals
  • Nitric oxide
  • Peroxynitrite

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