Based on corroborative observations from MCAO animal model and OGD cell model of ischemic stroke, the present study provided the first documentation that Pnn also protects astrocytes from apoptotic and necrotic cell death induced by ischemia via maintenance of mitochondrial anti-apoptotic (Bcl-2 upregulation) and bioenergetics functions. Here, BCL2 is linked to ischemic stroke.