PEROXYNITRITE FORMATION WITHIN THE CENTRAL-NERVOUS-SYSTEM IN ACTIVE MULTIPLE-SCLEROSIS

Peroxynitrite, generated by the reaction of nitric oxide (NO) with sup eroxide at sites of inflammation, is a strong oxidant capable of damag ing tissues and cells. Detection of nitrotyrosine (NT) at inflammatory sites serves as a biochemical marker for peroxynitrite-mediated damag e. In this study, NT was detected immunohistochemically within autopsi ed CNS tissues from six of nine multiple sclerosis (MS) patients, and in most of the MS sections displaying inflammation. Nitrite and nitrat e, the stable oxidation products of NO and peroxynitrite, respectively , were measured in cerebrospinal fluid samples obtained from MS patien ts and controls. Levels of nitrate were elevated significantly during clinical relapses of MS. These data suggest that peroxynitrite formati on isa major consequence of NO produced in MS-affected CNS and implica te a role for this powerful oxidant in the pathogenesis of MS. (C) 199 8 Published by Elsevier Science B.V. All rights reserved.