Mitochondrial Dysfunction in Ischemic Stroke
Mitochondrial Dysfunction in Ischemic Stroke
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DOI：
10.1007/978-981-10-5804-2_10
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Qiang-Lin Li;Shane Gao
中科院分区：
文献类型：
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作者：
Qiang-Lin Li;Shane Gao
线粒体是脑缺血再灌注后细胞存活的重要动力。线粒体是脑缺血再灌注损伤的敏感细胞器。线粒体功能障碍是脑缺血再灌注过程中最重要的事件之一，并对脑细胞造成进一步的损伤。它不仅影响缺血性脑卒中后神经细胞的命运，而且影响血脑屏障的通透性。线粒体功能障碍决定细胞存活和死亡的潜在机制涉及许多细胞信号通路，包括凋亡、自噬和线粒体生物发生。线粒体凋亡途径在过去被广泛探索。线粒体凋亡通路涉及许多凋亡相关调控家族，如Bcl-2家族、caspase家族、p53基因家族等。另一方面，脑缺血/再灌注后，ROS损伤、Ca2+超载和mPTP开放也对线粒体功能不利。线粒体自噬和线粒体生物发生在脑缺血/再灌注后细胞存活中的重要作用，被认为是线粒体功能障碍的内源性保护机制。因此，在缺血/再灌注条件下，促进内源性保护机制和抑制外源性损伤机制都是重要的治疗策略。总之，线粒体功能障碍不仅仅是缺血/再灌注损伤的结果，也是级联损伤的原因。因此，保护功能失调的线粒体是缺血性中风后细胞存活的关键。
Mitochondrion is the powerhouse of the cell, which is essential for cell survival after cerebral ischemia/reperfusion. Mitochondrion is a sensitive organelle susceptible to brain ischemia/reperfusion injury. Mitochondrial dysfunction is one of the foremost events involved in brain ischemia/reperfusion process and then induces further damage to brain cells. It influences not only the fate of neural cells but also blood-brain barrier permeability after ischemic stroke. The underlying mechanism of mitochondria dysfunction in determining cell survival and cell death involves in many cell signaling pathways including apoptosis, autophagy, and mitochondrial biogenesis. Mitochondria apoptosis pathway was extensively explored in the past. Many apoptosis-related regulator families were involved in mitochondria apoptosis pathway, like Bcl-2 family, caspase family, p53 gene family, and so on. On the other hand, ROS injury, Ca2+overload, and mPTP opening are also detrimental to mitochondrial function after cerebral ischemia/reperfusion. Recent interests were focused on the important role of mitophagy and mitochondrial biogenesis on cell survival after cerebral ischemia/reperfusion, which are thought to be endogenous protective mechanisms of mitochondrial dysfunction. Therefore, under ischemia/reperfusion conditions, promoting endogenous protective mechanisms and inhibiting exogenous damage mechanisms are both important therapeutic strategies. In summary, mitochondrial dysfunction is not simply the result of ischemia/reperfusion injury but also the cause of cascading damage. So, protecting dysfunctional mitochondria is pivotal to cell survival after ischemic stroke.