Jackson Charles W, Escobar Iris, Xu Jing, Perez-Pinzon Miguel A
Department of Neurology and Neuroscience Program, Cerebral Vascular Disease Research Laboratories, Miller School of Medicine, University of Miami, Miami, Florida, USA.
Brain Circ. 2018 Apr-Jun;4(2):54-61. doi: 10.4103/bc.bc_7_18. Epub 2018 Jun 29.
Stroke and cardiac arrest result in cerebral ischemia, a highly prevalent medical issue around the world, which is characterized by a reduction or loss of blood flow to the brain. The loss of adequate nutrient supply in the brain during ischemia results in neuronal cell death contributing to cognitive and motor deficits that are usually permanent. Current effective therapies for cerebral ischemia are only applicable after the fact. Thus, the development of preventative therapies of ischemia is imperative. A field of research that continues to show promise in developing therapies for cerebral ischemia is ischemic preconditioning (IPC). IPC is described as exposure to sublethal ischemic events, which induce adaptive changes that provide tolerance to future ischemic events. Through either transient sub-lethal ischemic events, or the actions of a preconditioning molecular mimetic, IPC typically results in augmented gene expression and cellular metabolism. A pivotal target of such changes in gene expression and metabolism is the mitochondrion. Direct and indirect effects on mitochondria by IPC can result in the activation of 5' adenosine monophosphate-activated protein kinase (AMPK), a master regulator of cellular metabolism. Changes in the activity of the posttranslational modifiers, SIRT1 and SIRT5, also contribute to the overall adaptive processes in cellular metabolism and mitochondrial functioning. In this review, we present recently collected evidence to highlight the neuroprotective interactions of mitochondria with AMPK, SIRT1, and SIRT5 in IPC. To produce this review, we utilized PubMed and previous reviews to target and to consolidate the relevant studies and lines of evidence.
中风和心脏骤停会导致脑缺血，这是一个在全球范围内高度普遍的医学问题，其特征是大脑血液供应减少或丧失。缺血期间大脑中充足营养供应的丧失会导致神经元细胞死亡，进而导致通常为永久性的认知和运动功能障碍。目前针对脑缺血的有效治疗方法仅在发病后适用。因此，开发缺血性预防疗法势在必行。在开发脑缺血治疗方法方面一直显示出前景的一个研究领域是缺血预处理（IPC）。IPC被描述为暴露于亚致死性缺血事件，这些事件会诱导适应性变化，从而使机体对未来的缺血事件产生耐受性。通过短暂的亚致死性缺血事件或预处理分子模拟物的作用，IPC通常会导致基因表达增强和细胞代谢增加。这种基因表达和代谢变化的一个关键靶点是线粒体。IPC对线粒体的直接和间接影响可导致5' 腺苷单磷酸激活蛋白激酶（AMPK）的激活，AMPK是细胞代谢的主要调节因子。翻译后修饰因子SIRT1和SIRT5活性的变化也有助于细胞代谢和线粒体功能的整体适应性过程。在这篇综述中，我们展示了最近收集的证据，以突出线粒体与AMPK、SIRT1和SIRT5在IPC中的神经保护相互作用。为撰写本综述，我们利用PubMed和以往的综述来定位和整合相关研究及证据线索。
