Mice overexpressing rat heat shock protein 70 are protected against cerebral infarction

Increased expression of heat shock protein 70 (HSP70) in the brain has been extensively documented in association with a variety of insults, including ischemia, and is suggested to play a role in cell survival and recovery af ter ischemic injury. To more directly assess the protective role of HSP70 d uring ischemic brain damage, we used transgenic mice overexpressing the rat HSP70 (HSP70tg mice). In contrast to wild-type (wt) littermates, high leve ls of HSP70 messenger RNA and protein were detected in brains of HSP70tg mi ce under normal conditions, and immunohistochemical analysis revealed prima rily neuronal expression of HSP70. Heterozygous HSP70tg mice and their wt l ittermates were subjected to permanent focal cerebral ischemia by intralumi nal blockade of the middle cerebral artery. Cerebral infarction after 6 hou rs of ischemia, as evaluated by Nissl staining, was significantly less in H SP70tg mice compared with wt mice. This reduction in infarction volume in H SP70tg mice was not attributable to an altered cardiovascular anatomy or to initial differences in body temperature or hemodynamic parameters. The HSP 70tg mice were still protected against cerebral infarction 24 hours after p ermanent focal ischemia. The data suggest that HSP70 can markedly protect t he brain against ischemic damage and that approaches aimed at inducing HSP7 0 may lead to new therapeutic interventions in cerebrovascular injuries.