Preconditioning-induced ischemic tolerance: a window into endogenous gearing for cerebroprotection.
Preconditioning-induced ischemic tolerance: a window into endogenous gearing for cerebroprotection.
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DOI：
10.1186/2040-7378-2-2
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发表时间：
2010-01-21
期刊：
影响因子：
--
通讯作者：
Tatlisumak T
中科院分区：
文献类型：
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作者：
Durukan A;Tatlisumak T
缺血耐受是指通过先前的亚致死性伤害性刺激(即，预适应)获得的对致命性缺血的一过性抵抗。这种适应性反应被认为是一种进化上保守的防御机制，在各种物种中都能观察到。在大多数器官系统，包括心脏、肾脏、肝脏和小肠，预适应即使不是全部的，也赋予了缺血耐受性。自从20世纪90年代初S首次在沙土鼠脑内进行了具有里程碑意义的脑缺血耐受实验演示以来，有关脑缺血耐受机制的基础科学知识有了很大的提高。各种有害刺激可以预先调节大脑，大概是通过一种共同的机制，即基因组重新编程。缺血耐受发生在两个不同的时间窗口。早期的耐受性可以在几分钟内实现，但也会在几小时内迅速减弱。延迟耐受会在数小时内形成，并持续数天。早期耐受的主要机制是膜受体的适应，而基因激活和随后的从头蛋白合成主导延迟耐受。在动物中，缺血预适应与强健的脑保护有关。在人类中，短暂性脑缺血发作可能是导致缺血耐受的预适应的临床相关性。因此，模仿这种独特的内源性保护过程的机制是预防中风的潜在策略。也许治疗中风的新疗法即将问世，就在我们的细胞里。
Ischemic tolerance defines transient resistance to lethal ischemia gained by a prior sublethal noxious stimulus (i.e., preconditioning). This adaptive response is thought to be an evolutionarily conserved defense mechanism, observed in a wide variety of species. Preconditioning confers ischemic tolerance if not in all, in most organ systems, including the heart, kidney, liver, and small intestine. Since the first landmark experimental demonstration of ischemic tolerance in the gerbil brain in early 1990's, basic scientific knowledge on the mechanisms of cerebral ischemic tolerance increased substantially. Various noxious stimuli can precondition the brain, presumably through a common mechanism, genomic reprogramming. Ischemic tolerance occurs in two temporally distinct windows. Early tolerance can be achieved within minutes, but wanes also rapidly, within hours. Delayed tolerance develops in hours and lasts for days. The main mechanism involved in early tolerance is adaptation of membrane receptors, whereas gene activation with subsequent de novo protein synthesis dominates delayed tolerance. Ischemic preconditioning is associated with robust cerebroprotection in animals. In humans, transient ischemic attacks may be the clinical correlate of preconditioning leading to ischemic tolerance. Mimicking the mechanisms of this unique endogenous protection process is therefore a potential strategy for stroke prevention. Perhaps new remedies for stroke are very close, right in our cells.