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

研究I：用细胞内记录法研究了缺氧和高钾条件下大鼠脑片海马CA 1区神经元的活动。缺氧（95%N_2-5%CO_2平衡）后，大多数神经元出现小的超极化、缓慢渐进的去极化和快速去极化。用电压依赖性K-^+通道阻断剂（4-氨基吡啶、四乙基铵、钡、铯）灌流和细胞内注射EGTA均不能阻断缺氧诱导的初始超极化。因此，缺氧诱导的超极化可能是由电压非依赖性K^+电导率的增加引起的，例如，ATP敏感和/或Na激活的K^+电导率。缓慢和渐进的去极化和快速去极化通过高钾介质灌流来模拟。在Ca^2+阻断剂存在下，细胞膜活性部分恢复， ...更多信息 即使在60 mM K^+加载1.5分钟后也不存在。这些事实表明，细胞外K^+水平缓慢增加，导致缺氧时细胞膜缓慢去极化，而额外的Ca^<2+>内流导致长时间缺氧时CA 1神经元细胞膜发生不可逆的变化。对于突触的传输，IPSPs消失，而不改变EPSPs缺氧。研究II：轻微的脑损伤造成一个小针一周前生产的小鼠不完全脑缺血。在戊巴比妥钠或氯胺酮麻醉下钳夹双侧颈动脉60 min，观察缺血后1周存活动物数，并与单纯麻醉组和假手术组比较。脑损伤组在戊巴比妥麻醉诱导的脑缺血后的存活率显著高于其他两组。然而，当氯胺酮麻醉期间施加脑缺血时，脑损伤小鼠的存活率的改善变得不明显。结果提示，脑损伤可能产生某些抗脑缺血因子或保护机制的作用，氯胺酮可拮抗脑损伤诱导的抗缺血活性，巴比妥类麻醉剂可增强脑损伤诱导的抗缺血活性少

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