School of Chemistry, Chemical Engineering, and Life Sciences, Wuhan University of Technology, Wuhan, 430070, China.
Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
Neurochem Res. 2022 Dec;47(12):3525-3542. doi: 10.1007/s11064-022-03697-8. Epub 2022 Aug 17.
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.
缺血性脑卒中是发病率和死亡率的主要原因之一，影响着全球数以百万计的人。不可避免的是，缺血后脑血液供应的中断可能会促进一连串的病理生理过程。此外，随后的血流恢复和再氧合可能会进一步加重脑组织损伤。虽然重组组织型纤溶酶原激活剂（rt-PA）是恢复血液灌注的唯一批准疗法，但再灌注损伤和狭窄的治疗时间窗口限制了其在大多数脑卒中患者中的应用。越来越多的证据表明，多种细胞死亡机制与脑缺血再灌注损伤有关，包括细胞凋亡、细胞坏死、坏死性凋亡、自噬、细胞焦亡、铁死亡等。因此，了解各种细胞死亡机制及其相互作用至关重要。在这篇综述中，我们总结了脑缺血再灌注损伤的各种信号通路，并详细阐述了不同机制之间的串扰。
