Premium
Protective role of the cytokine‐inducible isoform of nitric oxide synthase induction and nitrosative stress in experimental autoimmune encephalomyelitis of the DA rat
Author(s) -
Kahl Kai G.,
Zielasek Jürgen,
Uttenthal L. Otto,
Rodrigo Jose,
Toyka Klaus V.,
Schmidt Harald H.H.W.
Publication year - 2003
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10649
Subject(s) - experimental autoimmune encephalomyelitis , peroxynitrite , nitric oxide synthase , nitrotyrosine , nitric oxide , encephalomyelitis , immunology , superoxide dismutase , oxidative stress , multiple sclerosis , tristetraprolin , cytokine , medicine , superoxide , chemistry , endocrinology , biochemistry , enzyme , messenger rna , rna binding protein , gene
The pathogenic role of nitric oxide (NO) in multiple sclerosis (MS) remains controversial. Some groups have reported a pathogenic role of NO in experimental autoimmune encephalomyelitis (EAE), an animal model of some aspects of MS, whereas we and others have found a disease‐suppressive effect of NO in EAE. Because the previously used EAE models have a mainly monophasic inflammatory disease course, distinct from MS, we here studied EAE in the DA rat, which better models the demyelinating and relapsing disease course of human MS. The induction of EAE in DA rats led to 1) severe inflammatory infiltrates mainly in the lumbar spinal cord; 2) an up‐regulation of the activity of the cytokine‐inducible isoform of NO synthases (NOS‐II); and 3) increased tissue protein tyrosine nitration, as indicated by peroxynitrite (ONOO − ), as a marker of nitrosative stress. Sources of superoxide metabolism, i.e., NADPH oxidase, myeloperoxidase, and superoxide dismutase, remained unchanged. Early treatment of animals with aminoguanidine, a relatively selective inhibitor of NOS‐II, lowered nitrotyrosine immunoreactivity but at the same time led to more severe disease and pronounced inflammatory infiltrates in the lumbar spinal cord. Our results suggest a rather protective role of NOS‐II induction and nitrosative stress in EAE in DA rats and support the hypothesis of a disease‐mitigating immunomodulatory role of NO in this animal model of MS. © 2003 Wiley‐Liss, Inc.