Durukan Aysan, Tatlisumak Turgut
Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
Exp Transl Stroke Med. 2010 Jan 21;2(1):2. doi: 10.1186/2040-7378-2-2.
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.
缺血耐受是指通过先前的亚致死性有害刺激（即预处理）获得的对致死性缺血的短暂抵抗。这种适应性反应被认为是一种进化上保守的防御机制，在多种物种中都有观察到。预处理在大多数器官系统（包括心脏、肾脏、肝脏和小肠）中，即便不是在所有系统中，也能赋予缺血耐受。自20世纪90年代初在沙鼠脑中首次进行缺血耐受的标志性实验证明以来，关于脑缺血耐受机制的基础科学知识有了大幅增加。各种有害刺激都可以预处理大脑，推测是通过一种共同机制，即基因组重编程。缺血耐受出现在两个时间上不同的阶段。早期耐受可在数分钟内实现，但也会在数小时内迅速消退。延迟耐受在数小时内形成并持续数天。早期耐受涉及的主要机制是膜受体的适应性变化，而随后的基因激活和从头蛋白质合成则在延迟耐受中占主导地位。缺血预处理与动物体内强大的脑保护作用相关。在人类中，短暂性脑缺血发作可能是导致缺血耐受的预处理的临床对应情况。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一种潜在策略。也许治疗中风的新方法已经非常接近，就在我们的细胞之中。
