Overexpression of Heat Shock Protein 27 Reduces Cortical Damage after Cerebral Ischemia

Abstract

Heat shock protein 27 (HSP27) has a major role in mediating survival responses to a range of central nervous system insults, functioning as a protein chaperone, an antioxidant, and through inhibition of cell death pathways. We have used transgenic mice overexpressing HSP27 (HSP27tg) to examine the role of HSP27 in cerebral ischemia, using model of permanent middle cerebral artery occlusion (MCAO). Infarct size was evaluated using multislice T 2 -weighted anatomical magnetic resonance imaging (MRI) after 24 h. A significant reduction of 30% in infarct size was detected in HSP27tg animals compared with wild-type (WT) littermates. To gain some insight into the mechanisms contributing to cell death and its attenuation by HSP27, we monitored the effect of induction of c-jun and ATF3 on tissue survival in MCAO and their effects on the expression of endogenous mouse HSP25 and HSP70. It is important that, the c-jun induction seen at 4 h tended to be localized to regions that were salvageable in HSP27tg mice but became infarcted in WT animals. Our results provide support for the powerful neuroprotective effects of HSP27 in cerebral ischemia.

Hypothermia decreased the expression of heat shock proteins in neonatal rat model of hypoxic ischemic encephalopathy

“…Although they were originally described as proteins induced by Bheat shock,Ĥ SP respond to a variety of brain injuries, including hypoxic ischemia (Dienel et al 1986;Ferriero et al 1990;Dwyer and Nishimura 1992;Kinouchi et al 1993a, b;Currie et al 2000;Sharp et al 2000). The neuroprotective effect of HSP against ischemic stroke has been clearly demonstrated in transgenic mice models of HSP70 (Plumier et al 1997;Lee et al 2001;Tsuchiya et al 2003;Lee et al 2004;van der Weerd et al 2005) and HSP27 (van der Weerd et al 2010). Pharmacologic induction or intravenous administration of HSP70 also decreased the extent of infarct in rodent models of stroke (Lu et al 2002;Doeppner et al 2009;Zhan et al 2010).…”

Transcriptome network-based method to identify genes associated with unruptured intracranial aneurysms

“…The infarct size is detected to be reduced in overexpressing HSP27tg mice compared with wild-type littermates in cerebral ischemia condition. This result indicates that HSP27 has powerful neuroprotective effects in cerebral ischemia (van der Weerd et al, 2010). HSPB1 is also identified to be expressed as a candidate gene for IA by genetic mapping analysis (Weinsheimer et al, 2007).…”

Heat-Shock Proteins in Clinical Neurology

“…Exercise preconditioning induced neuroprotection after stroke, mediated by HSP-70 upregulation. Transgenic mice overexpressing HSP-27 and subjected to cerebral ischemia demonstrated neuroprotective benefits due to this overexpression [38]. Several clinical studies support the importance of regular physical exercise in stroke prevention [39,40].…”