Sequential activation of necroptosis and apoptosis cooperates to mediate vascular and neural pathology in stroke

Significance Necroptosis has been defined as a regulated cell death mechanism that can be activated under apoptosis deficient conditions. Here we show that necroptosis can be activated under brain ischemic conditions without inhibition of apoptosis. Furthermore, neuronal necroptosis can be followed by delayed apoptosis after the reduction of TAK1 under ischemic conditions. Our study demonstrates the complex interaction of apoptosis and necroptosis after ischemic brain insult and suggests the therapeutic targeting of RIPK1 kinase for the treatment of stroke.