Sublethal cerebral ischemia inhibits caspase-3 activation induced by subsequent prolonged ischemia in the C57black/Crj6 strain mouse

Caspase-3 activation has been implicated in ischemic neuronal death. In the present study, we examined if cerebral ischemic tolerance induced by suble thal ischemia is associated with an attenuation of caspase-3 activation in a mouse forebrain ischemia model. Forebrain ischemia in C57Black/Crj6 strai n mice was induced by bilateral common carotid artery occlusion (BCCAO) for 18 min. Two episodes of 6-min ischemia were carried out as preconditioning 48 and 72 h before the 18-min BCCAO. Caspase-3-like activity was determine d by fluorescently monitoring the release of amino-4-methylcoumarin from N- acetyl-Asp-Glu-Val-Asp-7-amino-4-methylcoumarin in the striatal protein ext racts at 4, 24, and 72 h after reperfusion. The results showed that the isc hemic preconditioning significantly attenuated caspase-3 activation at 4, 2 4, and 72 h after reperfusion, and reduced neuronal loss caused by the 18-m in ischemia as examined on the 7th day after reperfusion. The present resul ts suggest that the neuroprotection achieved by ischemic preconditioning is related to an attenuation of caspase-3 activation. (C) 2001 Elsevier Scien ce Ltd. All rights reserved.