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

Sunita Rajdev, Kazushi Hara, Yasuaki Kokubo, Ruben Mestril, Wolfgang Dillmann, Philip R. Weinstein, Frank R Sharp

Research output: Contribution to journalArticle

248 Scopus citations

Abstract

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 after ischemic injury. To more directly assess the protective role of HSP70 during ischemic brain damage, we used transgenic mice overexpressing the rat HSP70 (HSP70tg mice). In contrast to wild-type (wt) littermates, high levels of HSP70 messenger RNA and protein were detected in brains of HSP70tg mice under normal conditions, and immunohistochemical analysis revealed primarily neuronal expression of HSP70. Heterozygous HSP70tg mice and their wt littermates were subjected to permanent focal cerebral ischemia by intraluminal blockade of the middle cerebral artery. Cerebral infarction after 6 hours of ischemia, as evaluated by Nissl staining, was significantly less in HSP70tg mice compared with wt mice. This reduction in infarction volume in HSP70tg mice was not attributable to an altered cardiovascular anatomy or to initial differences in body temperature or hemodynamic parameters. The HSP70tg mice were still protected against cerebral infarction 24 hours after permanent focal ischemia. The data suggest that HSP70 can markedly protect the brain against ischemic damage and that approaches aimed at inducing HSP70 may lead to new therapeutic interventions in cerebrovascular injuries.

Original languageEnglish (US)
Pages (from-to)782-791
Number of pages10
JournalAnnals of Neurology
Volume47
Issue number6
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Neuroscience(all)

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