Molecular analysis for ischemic tolerance of neuron

脑缺血后神经元死亡和存活的机制是神经科学研究的热点之一。最近的研究强调了线粒体在缺血性神经元损伤中的重要作用，即线粒体功能障碍导致神经元坏死和凋亡。另一方面，缺血应激诱导神经元缺血耐受的研究已有报道，但其分子机制尚未阐明。在本研究中，我们使用了几种脑缺血模型，包括a。沙鼠中的短暂前脑缺血，B. 3-硝基丙酸诱导的大鼠纹状体损伤，c.永久性大脑中动脉闭塞大鼠，d.短暂性大脑中动脉闭塞大鼠，目的：研究线粒体功能与细胞凋亡的关系及缺血耐受的机制。模型a和B中神经元死亡与凋亡有关，模型B和c中神经元损伤与凋亡相关基因和聚腺苷二磷酸核糖化有关，模型c和d中缺血半暗带神经元硫氧还蛋白明显诱导，模型a和e中3-硝基丙酸化学预处理和硫氧还蛋白过表达可诱导缺血耐受。

The mechanisms of neuronal death and survival in ischemic brain are one of major topics in neuroscience. Recent papers have stressed the important role of mitochondria in ischemic neuronal damage in that both necrosis and apoptosis are induced by the dysfunction of mitochondria. On the other hand, the induction of ischemic tolerance in neuron after ischemic stress has been reported, but the molecular mechanisms of ischemic tolerance have not been elucidated. In the present study, we used several cerebral ischemic models including a. transient forebrain ischemia in gerbil, b. 3-nitropropionic acid-induced striatal damage in rat, c. permanent middle cerebral artery occlusion in rat, d. transient middle cerebral artery occlusion in rat, e. permanent middle cerebral artery occlusion in mouse in order to examine the relation of mitochondrial function and apoptosis and the mechanism of ischemic tolerance. We have demonstrated that apoptosis was involved in neuronal death in model a and b, that apoptosis related genes and poly(ADP-ribosyl)ation was involved in neuronal damage in model b and c, that thioredoxin is markedly induced in neuron in ischemic penumbra in model c and d, and that chemical preconditioning with 3-nitropropionic acid and overexpression of thioredoxin can induce ischemic tolerance in model a and e.