Wu Liquan, Xiong Xiaoxing, Wu Xiaomin, Ye Yingze, Jian Zhihong, Zhi Zeng, Gu Lijuan
Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, China.
Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China.
Front Mol Neurosci. 2020 Mar 5;13:28. doi: 10.3389/fnmol.2020.00028. eCollection 2020.
The cerebral ischemia injury can result in neuronal death and/or functional impairment, which leads to further damage and dysfunction after recovery of blood supply. Cerebral ischemia/reperfusion injury (CIRI) often causes irreversible brain damage and neuronal injury and death, which involves many complex pathological processes including oxidative stress, amino acid toxicity, the release of endogenous substances, inflammation and apoptosis. Oxidative stress and inflammation are interactive and play critical roles in ischemia/reperfusion injury in the brain. Oxidative stress is important in the pathological process of ischemic stroke and is critical for the cascade development of ischemic injury. Oxidative stress is caused by reactive oxygen species (ROS) during cerebral ischemia and is more likely to lead to cell death and ultimately brain death after reperfusion. During reperfusion especially, superoxide anion free radicals, hydroxyl free radicals, and nitric oxide (NO) are produced, which can cause lipid peroxidation, inflammation and cell apoptosis. Inflammation alters the balance between pro-inflammatory and anti-inflammatory factors in cerebral ischemic injury. Inflammatory factors can therefore stimulate or exacerbate inflammation and aggravate ischemic injury. Neuroprotective therapies for various stages of the cerebral ischemia cascade response have received widespread attention. At present, neuroprotective drugs mainly include free radical scavengers, anti-inflammatory agents, and anti-apoptotic agents. However, the molecular mechanisms of the interaction between oxidative stress and inflammation, and their interplay with different types of programmed cell death in ischemia/reperfusion injury are unclear. The development of a suitable method for combination therapy has become a hot topic.
脑缺血损伤可导致神经元死亡和/或功能障碍，这会在血供恢复后导致进一步的损伤和功能障碍。脑缺血/再灌注损伤（CIRI）常导致不可逆的脑损伤以及神经元损伤和死亡，其涉及许多复杂的病理过程，包括氧化应激、氨基酸毒性、内源性物质释放、炎症和细胞凋亡。氧化应激和炎症相互作用，在脑缺血/再灌注损伤中起关键作用。氧化应激在缺血性中风的病理过程中很重要，对缺血性损伤的级联发展至关重要。氧化应激是在脑缺血期间由活性氧（ROS）引起的，更有可能导致细胞死亡并最终在再灌注后导致脑死亡。特别是在再灌注期间，会产生超氧阴离子自由基、羟自由基和一氧化氮（NO），它们可导致脂质过氧化、炎症和细胞凋亡。炎症改变了脑缺血损伤中促炎和抗炎因子之间的平衡。因此，炎症因子可刺激或加剧炎症并加重缺血性损伤。针对脑缺血级联反应各个阶段的神经保护疗法受到了广泛关注。目前，神经保护药物主要包括自由基清除剂、抗炎剂和抗凋亡剂。然而，氧化应激与炎症之间相互作用的分子机制，以及它们在缺血/再灌注损伤中与不同类型程序性细胞死亡的相互作用尚不清楚。开发一种合适的联合治疗方法已成为一个热门话题。
