Clinical adoptable brain ischemic tolerance induced by modified electroconvulsive shock

许多研究者在动物模型中证明，轻微的应激如亚致死性缺血、热和皮层扩散性抑制可以使神经元对随后的致死性缺血损伤更耐受。尽管缺血耐受性的概念是至关重要的，但所有这些程序都过于侵入性而不能应用于临床。以往的动物实验表明，电休克（ECS）可引起神经元活动增强，引起热休克家族、即早基因和营养因子的快速分子反应，参与神经元缺血耐受的获得。在这项研究中，我们已经测试了大鼠的假设，ECS是一种有效的措施，以获得交叉耐受对随后的局灶性脑ischemia.Materials和方法：43只Wistar雄性大鼠随机分为以下四组之一。第一组接受重复ECS，每天一次，连续9天（rECS）。第二组接受单一ECS（sECS）。三重力加 ...更多信息 对照组（Control）。第四组为假手术组，在异氟醚-氧联合麻醉下，于麻醉苏醒前即刻经耳夹电极给予每一次50 mA，3.0s的电刺激。所有接受ECS治疗的动物均显示完全强直阵挛发作，随后为后肢伸展和昏迷期。在rECS和sECS组中，在末次ECS后2天诱导缺血。采用清醒状态下的大脑中动脉闭塞技术，缺血时间为45分钟。缺血2d后断头处死大鼠，TTC染色冠状面计算梗死体积。sECS组皮质和皮质下的梗死体积明显较小（分别为75.6+/-52.87 mm和53.69+/-18.98 mm）比对照组（分别为173.39+/-53.86 mm，p=0.0012和72.28+/-11.34 mm，p=0.0223）。rECS皮质梗死体积（112.4 ± 47.86 mm，p=0.0305）组梗死面积也明显小于对照组，而皮质下梗死面积（68.72+/-10.96 mm，p=0.6432）未显示显著减少。这些数据表明，缺血前48小时的ECS减少了致死性局灶性脑缺血的梗死体积。ECS可能作为一种新的预处理手术，其中暂时性缺血是不可避免的。少

Many investigators have demonstrated that minor stress such as sublethal ischemia, heat, and cortical spreading depression could make neurons more tolerant to subsequent lethal ischemic insults in animal model. Even though the concept of ischemic tolerance is crucial, all of these procedures are too invasive to be applied in clinical use. Previous animal studies have suggested that electroconvulsive shock(ECS) increases neuronal activities and then could cause rapid molecular responses of heat shock families, immediate early genes and trophic factors, which are involved to acquire neuronal ischemic tolerance. In this study we have tested in rats the hypothesis that ECS is an effective measure to acquire cross-tolerance against subsequent focal cerebral ischemia.Materials and Methods : 43 Wistar male rats were randomly allocated to one of the following four groups. First group received repeated ECS once a day for 9 consecutive days (rECS). Second group received single ECS(sECS). Third g … More roup of untreated with ECS rats were served as control (Control). Fourth group, which received sECS or rECS without ischemic insult, was prepared as a sham group(Sham).Every ECS(50mA,3.0s) was administered via ear-clip electrodes just before awakened from isoflurane-oxygen anesthesia. All animals treated with ECS showed a full tonic-clonic attack, followed by hind limb extension and stuporous phase. In rECS and sECS groups, ischemia was induced 2 days after the last ECS. The ischemic time was 45 minutes using intraluminal middle cerebral occlusion technique under awakeful status. 2 days after the ischemic insults, rats were sacrificed by decapitation, and the infarction volume was calculated in TTC stained coronal planes.Results : Infarction volumes in the cortex and subcortex were significantly smaller in the sECS group (75.6+/-52.87 mm, and 53.69+/-18.98mm, respectively) than those in the control group (173.39+/-53.86 mm p=0.0012 and 72.28+/-11.34 mm, p=0.0223 respectively). The infarct volume of cortex in the rECS(112.4+/-47.86 mm, p=0.0305) group was also significantly smaller, compared with that in the control group, while the infarct area of subcortex (68.72+/-10.96 mm, p=0.6432) did not show significant reduction.Conclusion : This data suggest that ECS at 48 hours before ischemia reduces the infarction volume subjected to lethal focal cerebral ischemia. ECS may have a possibility as a novel pretreatment for surgery in which temporary ischemia is unavoidable. Less