Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Signal Transduct Target Ther. 2022 Jul 6;7(1):215. doi: 10.1038/s41392-022-01064-1.
Ischemic stroke is caused primarily by an interruption in cerebral blood flow, which induces severe neural injuries, and is one of the leading causes of death and disability worldwide. Thus, it is of great necessity to further detailly elucidate the mechanisms of ischemic stroke and find out new therapies against the disease. In recent years, efforts have been made to understand the pathophysiology of ischemic stroke, including cellular excitotoxicity, oxidative stress, cell death processes, and neuroinflammation. In the meantime, a plethora of signaling pathways, either detrimental or neuroprotective, are also highly involved in the forementioned pathophysiology. These pathways are closely intertwined and form a complex signaling network. Also, these signaling pathways reveal therapeutic potential, as targeting these signaling pathways could possibly serve as therapeutic approaches against ischemic stroke. In this review, we describe the signaling pathways involved in ischemic stroke and categorize them based on the pathophysiological processes they participate in. Therapeutic approaches targeting these signaling pathways, which are associated with the pathophysiology mentioned above, are also discussed. Meanwhile, clinical trials regarding ischemic stroke, which potentially target the pathophysiology and the signaling pathways involved, are summarized in details. Conclusively, this review elucidated potential molecular mechanisms and related signaling pathways underlying ischemic stroke, and summarize the therapeutic approaches targeted various pathophysiology, with particular reference to clinical trials and future prospects for treating ischemic stroke.
缺血性脑卒中主要由脑血流中断引起,导致严重的神经损伤,是全球范围内导致死亡和残疾的主要原因之一。因此,深入阐明缺血性脑卒中的发病机制并寻找新的治疗方法具有重要意义。近年来,人们努力了解缺血性脑卒中的病理生理学,包括细胞兴奋性毒性、氧化应激、细胞死亡过程和神经炎症。同时,许多信号通路,无论是有害的还是神经保护的,也高度参与上述病理生理学。这些通路相互紧密交织,形成一个复杂的信号网络。此外,这些信号通路具有治疗潜力,因为针对这些信号通路可能成为治疗缺血性脑卒中的方法。在本综述中,我们描述了参与缺血性脑卒中的信号通路,并根据它们参与的病理生理过程对其进行分类。还讨论了针对上述病理生理学相关信号通路的治疗方法。同时,详细总结了与缺血性脑卒中相关的潜在治疗靶点的临床试验。总之,本综述阐明了缺血性脑卒中的潜在分子机制和相关信号通路,并总结了针对各种病理生理学的治疗方法,特别参考了临床试验和治疗缺血性脑卒中的未来前景。