BIOCHEMISTRY OF DELAYED NEURONAL DEATH AFTER ISCHEMIA

这项研究的长期目标是确定生物化学 损伤(S)，负责缺血后的细胞损伤。怎么回事？ 致病事件的发生，以及它发生的地点和时间，一直是 引起了一些争议。组织的命运可以被决定 但也有证据表明，氧气的重新引入 再循环中的葡萄糖会引起一种独特的代谢反应 这表明脑缺血后的恢复过程不仅仅是 逆转缺血诱发的事件。根据最近的观察，以下是 双侧脑缺血5分钟后大鼠大脑皮质CA1区锥体神经元 海马区再循环4天死亡提供了一个很好的模型 对细胞死亡前的生化事件的研究。这个 拟议的实验旨在1)检验 近全脑缺血对离散脑区远期恢复的影响 表现出不同程度的对缺血的脆弱性，以及2)测试 关于缺血细胞潜在原因的假说的数量 死亡。在这些活体实验中，高能的浓度 磷酸盐、葡萄糖代谢物、某些氨基酸和环状 核苷酸将在CA1和CA3区的胞体层被测量 海马体和大脑皮质的一部分 不同的间隔时间长达7天的再循环。组织样本 重量小于1微克，需要使用微量 代谢物测定的组织化学方法。离散型 组织采样应该能更准确地确定 在受影响的组织内发生的实际变化。在此基础上的变体 包括更长时间的缺血的选择性脆弱性模型， 戊巴比妥治疗和高血糖也将被检查。这个 结果应该定义与神经元死亡相关的病理生理学。 并提供对长期复苏过程的更多洞察力。这个 后者应为试验提供时间和生化基础 再循环期间的新治疗方法。

The long-term objective of this research is to identify the biochemical lesion(s) responsible for cell damage following ischemia. What the pathogenic event is, as well as where and when it occurs, has been the subject of some controversy. The fate of the tissue may be determined during ischemia, but there is also evidence that reintroduction of oxygen and glucose during recirculation elicits a unique metabolic response suggesting that the recovery process following ischemia is more than a reversal of ischemia-induced events. The recent observation that following 5 minutes of bilateral ischemia the CA 1 pyramidal neurons of the hippocampus die at 4 days of recirculation provides an excellent model for the investigation of the biochemical events that precede cell death. The proposed experiments are designed 1) to examine the effects of near-complete ischemia on long-term recovery in discrete brain regions which exhibit varying degrees of vulnerability to ischemia and 2) to test a number of hypotheses concerning the underlying causes of ischemic cell death. In these in vivo experiments, the concentrations of high-energy phosphates, glucose metabolites, certain amino acids and the cyclic nucleotides will be measured in the somal layer of the CA 1 and CA 3 region of the hippocampus as well as in a portion of the cerebral cortex at various intervals for up to 7 days of recirculation. The tissue samples weigh less than 1 ug and will require the use of microquantitative histochemical methods for the measurement of the metabolites. The discrete sampling of tissue should provide a more precise determination of the actual changes that occur within the affected tissue. Variations on this model of selective vulnerability including longer periods of ischemia, pentobarbital treatment and hyperglycemia will also be examined. The results should define the pathophysiology associated with neuronal death and provide additional insight into the long-term recovery process. The latter should give a temporal and a biochemical basis for the testing of novel therapeutic approaches during recirculation.