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Clinical adoptable brain ischemic tolerance induced by modified electroconvulsive shock

改良电休克诱导临床可采用的脑缺血耐受

基本信息

批准号：
14571477
负责人：
MIYAGAWA Yoshikado
金额：
$ 2.24万
依托单位：
Kurume University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571477/
关键词：
Ischemic tolerance electroconvulsive shock rat forebrain ischemia rat focal cerebral ischemia rat spinal cord ischemia model 電気痙攣療法

项目摘要

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

许多研究人员已经在动物模型中证明了轻微的应激，如亚致死性缺血、高温和皮质播散性抑制，可以使神经元对随后的致命性缺血损伤更耐受。尽管缺血耐受的概念至关重要，但所有这些手术都具有太大的侵入性，无法应用于临床。以往的动物研究表明，电休克可增加神经元的活性，进而引起热休克家族、即刻早期基因和营养因子的快速分子反应，参与获得神经元的缺血耐受。在本研究中，我们在大鼠身上验证了ECS是获得对随后的局灶性脑缺血的交叉耐受的有效措施的假设。材料和方法：Wistar雄性大鼠43只，随机分为以下四组。第一组接受重复ECS，每天一次，连续9天(REC)。第二组接受单一ECS(SECS)。第三代…另设多组未经ECS处理的大鼠为对照组。第4组为假手术组(Sham组)，分别在异氟醚-氧气复合麻醉苏醒前经耳夹电极注射50 mA、3.0 mA的ECS。所有接受ECS处理的动物都表现出完全的强直-阵挛发作，随后是后肢伸展和呆滞阶段。RECs组和SECs组在末次ECS后2天诱导缺血。清醒状态下采用大脑中动脉腔内阻断技术，缺血时间为45min。结果：与对照组(173.39+/-53.86mmp=0.0012)和(72.28+/-11.34mmp=0.0223)相比，SECS组大脑皮层和皮质下脑梗塞体积明显缩小(分别为75.60±52.87 mm和53.69±18.98 mm，p=0.0223)。与对照组相比，缺血前48h大脑皮层梗死体积(112.4+/-47.86 mm，p=0.0305)明显缩小，皮质下(68.72+/-10.96 mm，p=0.6432)梗死面积无明显缩小。ECS有可能作为一种新的手术前处理，在手术中暂时的缺血是不可避免的。较少