Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar, Gujarat, 382355, India.
Cellular and Molecular Neurobiology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar, Assam, India.
Transl Stroke Res. 2020 Dec;11(6):1185-1202. doi: 10.1007/s12975-020-00806-z. Epub 2020 Mar 26.
Ischemic stroke is one of the significant causes of morbidity and mortality, affecting millions of people across the globe. Cell injury in the infarct region is an inevitable consequence of focal cerebral ischemia. Subsequent reperfusion exacerbates the harmful effect and increases the infarct volume. These cellular injuries follow either a regulated pathway involving tightly structured signaling cascades and molecularly defined effector mechanisms or a non-regulated pathway, also known as accidental cell death, where the process is biologically uncontrolled. Classical cell death pathways are long established and well reported in several articles that majorly define apoptotic cell death. A recent focus on cell death study also considers investigation on non-classical pathways that are tightly regulated, may or may not involve caspases, but non-apoptotic. Pathological cell death is a cardinal feature of different neurodegenerative diseases. Although ischemia cannot be classified as a neurodegenerative disease, it is a cerebrovascular event where the infarct region exhibits aberrant cell death. Over the past few decades, several therapeutic options have been implicated for ischemic stroke. However, their use has been hampered owing to the number of limitations that they possess. Ischemic penumbral neurons undergo apoptosis and become dysfunctional; however, they are salvageable. Thus, understanding the role of different cell death pathways is crucial to aid in the modern treatment of protecting apoptotic neurons.
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群。梗死区域的细胞损伤是局灶性脑缺血的必然后果。随后的再灌注会加剧这种有害影响，增加梗死体积。这些细胞损伤要么遵循受调控的途径，涉及紧密构建的信号级联和分子定义的效应机制，要么遵循非受调控的途径，也称为意外细胞死亡，其中过程是生物不受控的。经典的细胞死亡途径在多篇文章中已经确立并得到广泛报道，这些文章主要定义了细胞凋亡。最近对细胞死亡研究的关注还考虑了对受紧密调控的非经典途径的研究，这些途径可能涉及或不涉及半胱天冬酶，但非凋亡。病理性细胞死亡是多种神经退行性疾病的主要特征。尽管缺血不能被归类为神经退行性疾病，但它是一种脑血管事件，其中梗死区域表现出异常的细胞死亡。在过去的几十年中，已经提出了几种治疗缺血性脑卒中的方法。然而，由于它们存在许多限制，其应用受到了阻碍。缺血半影区的神经元经历细胞凋亡并变得功能失调；然而，它们是可挽救的。因此，了解不同细胞死亡途径的作用对于帮助现代治疗中保护凋亡神经元至关重要。
