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Study on pathophysiology of cerebral hypoxia by means of the brain slice technique and the regional perfusion technique

脑切片技术和局部灌注技术研究脑缺氧的病理生理学

基本信息

批准号：
60480345
负责人：
SHIMOJI Koki
金额：
$ 4.16万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1987
项目状态：
已结题

项目摘要

Study I: The activities of the hippocampal CAl neurons in rat brain slices were investigated by intracellular recording under hypoxic and high potassium conditions of superfuson media. By superfusion of the hypoxic (95%N_2-5%CO_2 equilibrated) medium, a small hyperpolarization, a slow and gradual depolarization and a rapid depolarization were spquentially oserved in a majority of the neurons. The initial hyperpolarization induced by hypoxia was not blocked by superfusion with voltage-dependent K-^+-channel blockers (4-aminopyridine, tetraethylammonium, barium, cesium) and by intracellural injection of EGTA. Therefore, The hypoxia-induced hyperpolarization may be brought about by the increase in voltage-independent K^+ conductivities, e.g., ATP-sensitive and/or Na-activated K^+ conductivities. The slow and gradual depolarization and the rapid depolarization were mimicked by superfusion with high pottasium media. In the presence of Ca^<2+> blockers, the membrane activities partially rema … More ined even after 1.5min of 60mM K^+ loading. These facts suggest that the extracellulae K^+ level increases slowly to cause slow membrane depolarization with hypoxia, and that the additional Ca^<2+> influx causes irreversible change in the membrane of CAl neurons during prolonged hypoxia. For synaptic transmissions, IPSPs disappeared without change in EPSPs under hypoxia.Study II: Minor brain injury was inflicted with a small needle one week before the production of incomplete brain ischemia in the mouse. A bilateral carotid clamp was applied for 60 min under pentobarbital or ketamine anesthesia, and the number of survivors in one week after the ischemic insult was compared with those in animals anesthetized only and a sham-oparated group. Survival rates following the brain ischemia induced during pentobarbital anesthesia were significantly higher in the brain injured group than in the other two groups. However, the improvement of the survival rates in mice with brain injury became insignificant when brain ischemia was imposed during ketamine anesthesia. The results suggest that the actions of certain factors or protective mechanisms against brain ischemia were developed by brain injury and that the brain injury-induced anti-ischemic activity is antagonized by ketamine and/or potentiated by barbiturate anesthesea. Less

研究一：采用细胞内记录的方法，观察在低氧和高钾条件下，大鼠脑片中海马神经元的活动。通过低氧(95%N_2-5%CO_2平衡)介质的灌流，大多数神经元出现了小的超极化、缓慢和逐渐的去极化以及快速的去极化。电压依赖性钾通道阻滞剂(4-氨基吡啶、四乙基铵、钡、铯)灌流和细胞内注射EGTA均不能阻断缺氧引起的初始超极化。因此，低氧诱导的超极化可能是由于电压非依赖性K^+电导率的增加所致，如ATP敏感和/或Na激活的K^+电导。用高钾液灌流模拟慢、渐进性去极化和快速去极化。在Ca~(2+)阻断剂存在下，膜活性部分恢复…即使在60 mm K^+加载1.5分钟后，也会更加紧张。提示缺氧时细胞外K~(++)水平缓慢升高，导致膜去极化缓慢，而额外的Ca~(2+)内流可导致长时间缺氧时细胞膜发生不可逆转的变化。对于突触传递，在低氧条件下，IPSP消失，EPSP没有变化。研究II：在小鼠产生不完全性脑缺血前一周，用小针造成轻微脑损伤。在戊巴比妥或氯胺酮麻醉下夹闭双侧颈总动脉60min，并与单纯麻醉组和假手术组比较。在戊巴比妥钠麻醉诱导脑缺血后，脑损伤组的存活率明显高于其他两组。然而，在氯胺酮麻醉期间实施脑缺血对脑损伤小鼠存活率的改善作用不明显。结果提示，某些因素或保护机制对脑缺血的保护作用是由脑损伤引起的，氯胺酮和/或巴比妥类麻醉剂可拮抗脑损伤所致的抗脑缺血作用。较少