Cerebral Vascular Disease Research Center, Department of Neurology, University of Miami, Miller School of Medicine, Miami, Fl 33136.
Curr Neuropharmacol. 2012 Dec;10(4):354-69. doi: 10.2174/157015912804143577.
There is extensive evidence that the restoration of blood flow following cerebral ischemia contributes greatly to the pathophysiology of ischemia mediated brain injury. The initiating stimulus of reperfusion injury is believed to be the excessive production of reactive oxygen (ROS) and nitrogen (RNS) species by the mitochondria. ROS and RNS generation leads to mitochondrial protein, lipid and DNA oxidation which impedes normal mitochondrial physiology and initiates cellular death pathways. However not all ROS and RNS production is detrimental. It has been demonstrated that low levels of ROS production are protective and may serve as a trigger for activation of ischemic preconditioning. Ischemic preconditioning is a neuroprotective mechanism which is activated upon a brief sublethal ischemic exposure and is sufficient to provide protection against a subsequent lethal ischemic insult. Numerous proteins and signaling pathways have been implicated in the ischemic preconditioning neuroprotective response. In this review we examine the origin and mechanisms of ROS and RNS production following ischemic/reperfusion and the role of free radicals in modulating proteins associated with ischemic preconditioning neuroprotection.
有大量证据表明，脑缺血后血流的恢复对缺血介导的脑损伤的病理生理学有很大贡献。再灌注损伤的起始刺激因子被认为是线粒体中活性氧（ROS）和活性氮（RNS）物质的过度产生。ROS 和 RNS 的产生导致线粒体蛋白、脂质和 DNA 氧化，从而阻碍正常的线粒体生理学并启动细胞死亡途径。然而，并非所有的 ROS 和 RNS 产生都是有害的。已经证明，低水平的 ROS 产生具有保护作用，并且可以作为缺血预处理激活的触发因素。缺血预处理是一种神经保护机制，在短暂的亚致死性缺血暴露时被激活，足以提供对随后的致死性缺血损伤的保护。许多蛋白质和信号通路都与缺血预处理的神经保护反应有关。在这篇综述中，我们研究了缺血/再灌注后 ROS 和 RNS 产生的起源和机制，以及自由基在调节与缺血预处理神经保护相关的蛋白质中的作用。
