Ischemic stroke caused by arterial occlusion is the most common type of stroke, which is among the most frequent causes of disability and death worldwide. Current treatment approaches involve achieving rapid reperfusion either pharmacologically or surgically, both of which are time-sensitive; moreover, blood flow recanalization often causes ischemia/reperfusion injury. However, even though neuroprotective intervention is urgently needed in the event of stroke, the exact mechanisms of neuronal death during ischemic stroke are still unclear, and consequently, the capacity for drug development has remained limited. Multiple cell death pathways are implicated in the pathogenesis of ischemic stroke. Here, we have reviewed these potential neuronal death pathways, including intrinsic and extrinsic apoptosis, necroptosis, autophagy, ferroptosis, parthanatos, phagoptosis, and pyroptosis. We have also reviewed the latest results of pharmacological studies on ischemic stroke and summarized emerging drug targets with a focus on clinical trials. These observations may help to further understand the pathological events in ischemic stroke and bridge the gap between basic and translational research to reveal novel neuroprotective interventions.

中文翻译：

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缺血性卒中神经元细胞死亡的机制及其治疗意义

由动脉闭塞引起的缺血性中风是最常见的中风类型，是全球最常见的致残和死亡原因之一。目前的治疗方法包括通过药物或手术实现快速再灌注，这两种方法都是时间敏感的；此外，血流再通常引起缺血/再灌注损伤。然而，即使在中风事件中迫切需要神经保护干预，但缺血性中风期间神经元死亡的确切机制仍不清楚，因此药物开发能力仍然有限。多种细胞死亡途径与缺血性中风的发病机制有关。在这里，我们回顾了这些潜在的神经元死亡途径，包括内在和外在细胞凋亡、坏死性凋亡、自噬、铁死亡、parthanatos, phagoptosis, 和 pyroptosis。我们还回顾了缺血性卒中药理学研究的最新结果，并总结了以临床试验为重点的新兴药物靶点。这些观察结果可能有助于进一步了解缺血性中风的病理事件，并弥合基础研究和转化研究之间的差距，以揭示新的神经保护干预措施。