Macdonald R L, Stoodley M
Section of Neurosurgery, University of Chicago Medical Center, Illinois, USA.
Neurol Med Chir (Tokyo). 1998 Jan;38(1):1-11. doi: 10.2176/nmc.38.1.
The purpose of this manuscript is to briefly review the pathophysiology of cerebral ischemia. Ischemic thresholds are well-defined in lower animals. The concept of the ischemic penumbra may include regions of brain around deeper regions of ischemia but has also been defined in terms of brain salvageable by reperfusion or by pharmacological therapies. The principal pathophysiological processes in cerebral ischemia are energy failure, loss of cell ion homeostasis, acidosis, increased intracellular calcium, excitotoxicity, and free radical-mediated toxicity. The underlying biochemical processes are similar regardless of the amount of brain that is made ischemic or the duration of ischemia. The relative contributions of each process are believed to vary significantly especially in relation to the level of cerebral blood flow. Neurons may die by necrosis or apoptosis. In the core of an infarct where blood flow is very low, the predominant process is energy failure and rapid necrotic cell death. Reperfusion of ischemic tissue produces an influx of inflammatory cells and of oxygen that can cause increases in oxygen-derived free radicals. Free radicals are also important in prolonged ischemia. There is interest in changes in gene expression after ischemia. Induction of heat shock proteins suggests that gene expression changes may protect neurons from death. Changes in gene expression also may initiate apoptosis or other detrimental processes. Although advances have been made, there are still no proven pharmacological therapies to rescue ischemic human neurons. Such therapies do appear to be on the horizon.
本手稿的目的是简要回顾脑缺血的病理生理学。缺血阈值在低等动物中已得到明确界定。缺血半暗带的概念可能包括缺血较深区域周围的脑区，但也可根据通过再灌注或药物治疗可挽救的脑区来定义。脑缺血的主要病理生理过程包括能量衰竭、细胞离子稳态丧失、酸中毒、细胞内钙增加、兴奋性毒性和自由基介导的毒性。无论缺血脑区的大小或缺血持续时间如何，其潜在的生化过程都是相似的。据信，每个过程的相对贡献差异很大，尤其是与脑血流量水平有关。神经元可能因坏死或凋亡而死亡。在梗死核心区，血流非常低，主要过程是能量衰竭和快速的坏死性细胞死亡。缺血组织的再灌注会导致炎症细胞和氧的流入，从而导致氧衍生自由基增加。自由基在长时间缺血中也很重要。人们对缺血后基因表达的变化很感兴趣。热休克蛋白的诱导表明基因表达变化可能保护神经元免于死亡。基因表达的变化也可能引发凋亡或其他有害过程。尽管已经取得了进展，但仍然没有经过证实的药物疗法来挽救缺血的人类神经元。不过这类疗法似乎即将出现。
