Sharp F R, Lu A, Tang Y, Millhorn D E
Department of Neurology, University of Cincinnati, Ohio 45267-0536, USA.
J Cereb Blood Flow Metab. 2000 Jul;20(7):1011-32. doi: 10.1097/00004647-200007000-00001.
Though the ischemic penumbra has been classically described on the basis of blood flow and physiologic parameters, a variety of ischemic penumbras can be described in molecular terms. Apoptosis-related genes induced after focal ischemia may contribute to cell death in the core and the selective cell death adjacent to an infarct. The HSP70 heat shock protein is induced in glia at the edges of an infarct and in neurons often at some distance from the infarct. HSP70 proteins are induced in cells in response to denatured proteins that occur as a result of temporary energy failure. Hypoxia-inducible factor (HIF) is also induced after focal ischemia in regions that can extend beyond the HSP70 induction. The region of HIF induction is proposed to represent the areas of decreased cerebral blood flow and decreased oxygen delivery. Immediate early genes are induced in cortex, hippocampus, thalamus, and other brain regions. These distant changes in gene expression occur because of ischemia-induced spreading depression or depolarization and could contribute to plastic changes in brain after stroke.
尽管缺血半暗带一直是根据血流和生理参数进行经典描述的，但也可以从分子角度描述多种缺血半暗带。局灶性缺血后诱导的凋亡相关基因可能导致梗死核心区的细胞死亡以及梗死灶周边的选择性细胞死亡。热休克蛋白70（HSP70）在梗死灶边缘的胶质细胞以及通常在距梗死灶一定距离的神经元中被诱导产生。HSP70蛋白是细胞对因暂时能量衰竭而出现的变性蛋白做出的反应而被诱导产生的。缺氧诱导因子（HIF）在局灶性缺血后也会在超出HSP70诱导范围的区域被诱导产生。HIF诱导区域被认为代表脑血流量减少和氧输送减少的区域。即刻早期基因在皮质、海马、丘脑和其他脑区被诱导产生。这些基因表达的远距离变化是由缺血诱导的扩散性抑制或去极化引起的，可能有助于中风后脑的可塑性变化。
