Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Center for Neuroscience Research, Loma Linda University School of Medicine, Loma Linda, CA, USA.
Curr Neuropharmacol. 2023;21(2):392-408. doi: 10.2174/1570159X20666220420115925.
Spontaneous subarachnoid hemorrhage (SAH), primarily caused by ruptured intracranial aneurysms, remains a prominent clinical challenge with a high rate of mortality and morbidity worldwide. Accumulating clinical trials aiming at the prevention of cerebral vasospasm (CVS) have failed to improve the clinical outcome of patients with SAH. Therefore, a growing number of studies have shifted focus to the pathophysiological changes that occur during the periods of early brain injury (EBI). New pharmacological agents aiming to alleviate EBI have become a promising direction to improve outcomes after SAH. Caspases belong to a family of cysteine proteases with diverse functions involved in maintaining metabolism, autophagy, tissue differentiation, regeneration, and neural development. Increasing evidence shows that caspases play a critical role in brain pathology after SAH. Therefore, caspase regulation could be a potential target for SAH treatment. Herein, we provide an overview pertaining to the current knowledge on the role of caspases in EBI after SAH, and we discuss the promising therapeutic value of caspase-related agents after SAH.
自发性蛛网膜下腔出血（SAH）主要由颅内破裂动脉瘤引起，是全球范围内死亡率和发病率都很高的突出临床挑战。旨在预防脑血管痉挛（CVS）的大量临床试验未能改善 SAH 患者的临床预后。因此，越来越多的研究将重点转移到早期脑损伤（EBI）期间发生的病理生理变化上。旨在减轻 EBI 的新型药理学药物已成为改善 SAH 后结局的有希望的方向。半胱氨酸蛋白酶家族属于半胱氨酸蛋白酶家族，具有多种功能，涉及维持代谢、自噬、组织分化、再生和神经发育。越来越多的证据表明，半胱天冬酶在 SAH 后的脑病理中起着关键作用。因此，半胱天冬酶的调节可能是 SAH 治疗的一个潜在靶点。本文就半胱天冬酶在 SAH 后 EBI 中的作用的最新知识进行综述，并讨论了与半胱天冬酶相关的药物在 SAH 后的潜在治疗价值。
