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Thrombin in ischemic neuronal death

By M. de Castro Ribeiro, J. Badaut, M. Price, M. Meins, J. Bogousslavsky, D. Monard and L. Hirt

Abstract

Thrombin plays a role in cerebral ischemia as rats subjected to focal cerebral ischemia were protected by the intracerebral injection of hirudin, a selective thrombin inhibitor. To separate the roles of thrombin in cell death and in coagulation, we have used an in vitro approach to test the effect of hirudin and of protease nexin-1 (PN-1), a cerebral thrombin inhibitor, on neuronal ischemia. Rat organotypic hippocampal slice cultures were subjected to oxygen (5%) and glucose (1 mmol/L) deprivation (OGD) during 30 min. Hirudin or PN-1 administered after OGD significantly prevented neuronal death in the CA1 region. After 24 h, there was a marked increase in thrombin immunoreactivity on Western blots. Thrombin therefore contributes to ischemic damage in neural tissue in vitro

Topics: Animals Animals, Newborn Anoxia/complications/drug therapy Blotting, Western/methods Cell Death/drug effects/physiology Disease Models, Animal Dose-Response Relationship, Drug Gene Expression Regulation/drug effects Glucose/deficiency Hippocampus/pathology Hirudin Therapy/methods Hirudins/pharmacology Ischemia/etiology/metabolism/*pathology/prevention & control Neurons/drug effects/metabolism Protease Inhibitors/pharmacology Rats Rats, Sprague-Dawley Thrombin/antagonists & inhibitors/*physiology
Year: 2006
DOI identifier: 10.1016/j.expneurol.2005.11.017
OAI identifier: oai:serval.unil.ch:BIB_1EB2BE6DEA93
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