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Heat shock protein A12B (HSPA12B) is the newest member of a recently defined subfamily of proteins distantly related to the 70-kDa family of heat shock proteins (HSP70) family.HSP70s play a crucial role in protecting cells, tissues, organs and animals from various noxious conditions.Here we studied the dynamic expression changes and localization of HSPA12B after middle cerebral artery occlusion (MCAO) with reperfusion induced ischemic insult processes in adult rats.Apoptosis, as indicated by TUNEL staining, was also increased in the peri-ischemic cortex compared to non-ischemic hemisphere.The expression of HSPA12B was strongly induced in the ischemic hemisphere of MCAO reperfusion rats in vivo.In vitro studies indicated that the up-regulation of HSPA12B may be involved in oxygen-glucose deprivation (OGD)-induced PC12 cell death.And knockdown of HSPA12B in cultured differentiated PC12 cells by siRNA showed that HSPA12B inhibited the expression of active caspase-3.Collectively, these results suggested that HSPA12B may be required for protecting neurons from ischemic insults.Our research may provide a novel strategy to facilitate neuroprotection against cerebral ischemic injury and several neurodegenerative diseases in central nervous system (CNS).