HSPA12B Is A Novel Neuroprotective Heat Shock Protein Against Focal Cerebral Ischemia/reperfusion

Background and Purpose:HSPA12B is a novel heat shock protein that is predominantly expressed in endothelial cells. This study investigated the effects of HSPA12B on cerebral ischemic injury in mice.Methods:Transgenic mice overexpressing human HSPA12B (Tg) and wild-type littermates (WT) were subjected to60minutes of middle cerebral artery occlusion followed by24hours of reperfusion (I/R). Neurological deficits, infarct volumes, neuronal death and blood-brain-barrier (BBB) integrity were examined. Activated cellular signaling was examined by immunoblot analysis.Results:Following I/R, Tg mice exhibited improvements in neurological deficits and had reduced infarct volumes compared with WT mice. These improvements were accompanied by a significant decrease in neuronal death, which was associated with an increased ratio of Bcl-2/Bax and decreased activation of JNKs and p38in Tg brains. BBB integrity was also significantly better maintained in Tg mice following I/R and was positively correlated with increased levels of angiopoietin-1, ZO-1and ZO-2.Conclusions:These results indicate an important role for HSPA12B in prevention of cerebral ischemia/reperfusion injury and suggest a possibility for the clinical use of this heat shock protein in ischemic stroke.