Cell Death Mechanisms in Cerebral Ischemia–Reperfusion Injury

Ischemic stroke is one of the major causes of morbidity and mortality, affecting millions of people worldwide. Inevitably, the interruption of cerebral blood supply after ischemia may promote a cascade of pathophysiological processes. Moreover, the subsequent restoration of blood flow and reoxygenation may further aggravate brain tissue injury. Although recombinant tissue plasminogen activator (rt-PA) is the only approved therapy for restoring blood perfusion, the reperfusion injury and the narrow therapeutic time window restrict its application for most stroke patients. Increasing evidence indicates that multiple cell death mechanisms are relevant to cerebral ischemia–reperfusion injury, including apoptosis, necrosis, necroptosis, autophagy, pyroptosis, ferroptosis, and so on. Therefore, it is crucial to comprehend various cell death mechanisms and their interactions. In this review, we summarize the various signaling pathways underlying cerebral ischemia–reperfusion injury and elaborate on the crosstalk between the different mechanisms.