Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda-151001,India.
CNS Neurol Disord Drug Targets. 2022;21(1):52-61. doi: 10.2174/1871527320666210212141232.
Stroke is the second most common cause of death worldwide. It occurs due to the insufficient supply of oxygen-rich blood to the brain. It is a complex disease with multiple associated risk factors, including smoking, alcoholism, age, sex, ethnicity, etc. Calcium ions are known to play a vital role in cell death pathways, which is a ubiquitous intracellular messenger during and immediately after an ischemic period. Disruption in normal calcium homeostasis is known to be a major initiator and activator of the ischemic cell death pathway. Under ischemic stroke conditions, glutamate is released from the neurons and glia, which further activates the N-methyl-D-aspartate (NMDA) receptor and triggers the rapid translocation of Ca2+ from extracellular to intracellular spaces in cerebral tissues and vice versa. Various studies indicated that Ca2+ could have harmful effects on neurons under acute ischemic conditions. Mitochondrial dysfunction also contributes to delayed neuronal death, and it was established decades ago that massive calcium accumulation triggers mitochondrial damage. Elevated Ca2+ levels cause mitochondria to swell and release their contents. As a result, oxidative stress and mitochondrial calcium accumulation activate mitochondrial permeability transition and lead to depolarization-coupled production of reactive oxygen species. This association between calcium levels and mitochondrial death suggests that elevated calcium levels might have a role in the neurological outcome in ischemic stroke. Previous studies have also reported that elevated Ca2+ levels play a role in the determination of infarct size, outcome, and recurrence of ischemic stroke. The current review has been compiled to understand the multidimensional role of altered Ca2+ levels in the initiation and alteration of neuronal death after an ischemic attack. The underlying mechanisms understood to date have also been discussed.
中风是全球范围内第二大致死原因。它是由于大脑供氧不足引起的。这是一种复杂的疾病，有多种相关的危险因素，包括吸烟、酗酒、年龄、性别、种族等。钙离子被认为在细胞死亡途径中起着至关重要的作用，它是缺血期及之后即刻细胞内普遍存在的信使。正常钙稳态的破坏被认为是缺血性细胞死亡途径的主要启动子和激活剂。在缺血性中风的情况下，谷氨酸从神经元和神经胶质细胞中释放出来，进一步激活 N-甲基-D-天冬氨酸（NMDA）受体，并触发大脑组织中细胞外 Ca2+快速向细胞内转移，反之亦然。各种研究表明，在急性缺血条件下，Ca2+可能对神经元产生有害影响。线粒体功能障碍也导致神经元延迟死亡，几十年前就已确定大量钙积累会引发线粒体损伤。Ca2+水平升高会导致线粒体肿胀并释放其内容物。结果，氧化应激和线粒体钙积累激活线粒体通透性转换，并导致去极化偶联的活性氧产生。钙水平与线粒体死亡之间的这种关联表明，升高的钙水平可能在缺血性中风的神经学结果中发挥作用。先前的研究还报告称，升高的 Ca2+水平在确定梗塞面积、结局和缺血性中风的复发中起作用。本综述旨在了解 Ca2+水平改变在缺血攻击后神经元死亡的启动和改变中的多维作用。还讨论了迄今为止理解的潜在机制。
