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Cortical spreading depression induces proinflammatory cytokine gene expression in the rat brain

Item Type:Article
Title:Cortical spreading depression induces proinflammatory cytokine gene expression in the rat brain
Creators Name:Jander, S. and Schroeter, M. and Peters, O. and Witte, O.W. and Stoll, G.
Abstract:Cortical spreading depression (CSD) is characterized by reversible neuronal dysfunction in the absence of cell death. Preconditioning by CSD induces tolerance against subsequent lethal ischemia. In this study, we used quantitative reverse transcriptase-polymerase chain reaction and immunocytochemistry to analyze proinflammatory cytokine expression after CSD induced by topical application of potassium chloride (KCl) to the cortical surface of rat brains. Relative to control cortex, we found an increase of tumor necrosis factor-alpha (mean 62-fold, P < 0.001) and interleukin (IL)-1beta (mean 24-fold, P < 0.001) mRNA levels within 4 hours ipsilateral to the site of KCl application. At 16 hours cytokine expression was decreasing toward baseline levels. Ipsilateral cytokine induction was abolished by pretreatment with the noncompetitive N-methyl-d-aspartate antagonist, MK-801. In contrast to focal cortical infarction, cytokine induction in CSD was not accompanied by the expression of inducible nitric oxide synthase mRNA. In immunocytochemical studies, expression of IL-1beta protein was localized to ramified microglia in cortical layers I to III of the ipsilateral hemisphere. Our finding that NMDA receptor signaling without subsequent neuronal cell death is sufficient to induce inflammatory cytokine expression in the brain has basic implications for central nervous system immunoregulation. We postulate that cytokine expression in CSD forms part of a physiologic stress response that contributes to the development of ischemic tolerance in this and other preconditioning paradigms.
Keywords:Central Nervous System, Spreading Depression, NMDA Receptor, Cytokine, Nitric Oxide Synthase, Ischemic Tolerance, Animals, Rats, Wistar Rats
Source:Journal of Cerebral Blood Flow and Metabolism
Publisher:Nature Publishing Group
Page Range:218-225
Date:March 2001
Official Publication:https://doi.org/10.1097/00004647-200103000-00005
PubMed:View item in PubMed

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