Thrombin in ischemic neuronal death.
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.
de Castro Ribeiro
Marlise
M
Neurology Service, BH 19 208, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.
Badaut
Jérôme
J
Price
Melanie
M
Meins
Marita
M
Bogousslavsky
Julien
J
Monard
Denis
D
Hirt
Lorenz
L
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000172:deficiency; D006624:Hippocampus / Q000473:pathology; D024764:Hirudin Therapy / Q000379:methods; D006629:Hirudins / Q000494:pharmacology; D000860:Hypoxia / Q000150:complications / Q000188:drug therapy; D066298:In Vitro Techniques; D007511:Ischemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000502:physiology*
D006629:Hirudins; D011480:Protease Inhibitors; D013917:Thrombin; D005947:Glucose