BIOCHEMISTRY OF DELAYED NEURONAL DEATH AFTER ISCHEMIA

这项研究的长期目标是确定 生化损伤(S)，对细胞损伤负责 缺血性发作。致病事件是什么，以及发生在哪里 而当它发生时，一直是一些争议的主题。这个 组织的命运可能在缺血期间决定，但有 也有证据表明，氧气和葡萄糖的重新引入会引起 独特的代谢反应，表明恢复过程是 这不仅仅是对缺血引起的事件的逆转。观察到的 前额叶中的整个CA1神经元群 海马区在5分钟后再循环4天死亡 沙土鼠双侧缺血提供了一种可复制的反应 调查细胞死亡前的生化事件。 拟议的实验旨在：1)检查影响 短暂性脑缺血对脑长期代谢恢复的影响 表现出不同程度的缺血敏感性的区域， 2)测试一些当前关于 缺血性细胞死亡和迟发性神经元死亡的发病机制 3)进一步评价GABA能神经保护作用 探员们。在这些活体实验中，高能水平 磷酸盐、葡萄糖相关代谢物、环核苷酸和 某些氨基酸神经递质将在索马尔进行测量 海马区和大脑皮质CA1和CA3区的层 在双侧5分钟后的不同时间进行再循环 缺血症。组织样本重约1微克， 将需要微量组织化学方法来测量 在pmole范围内的代谢产物。最后，CA的损失 1双侧脑缺血5分钟后复流4天的神经元 大大增加了这一区域的神经胶质细胞与神经元的比率。这 神经元耗竭区域将在第二次手术期间进行检查 缺血和再循环以确定A 富含胶质细胞的组织对缺血的反应。一个更健谈的人 已经证实了缺血时的酸化，但 胶质细胞中的代谢相关性还没有被研究过。这个 胶质细胞中酸碱平衡的重要性可以很好地解释 缺血细胞损伤的演变。延时的自然历史 神经元死亡将更好地用这些离散的 测量结果，预计该信息将有助于 作为测试新疗法的时间和生化指南 中风的治疗方法。

The long-term objective of this research is to identify the biochemical lesion(s) responsible for cell damage following an ischemic episode. 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 elicits a unique metabolic response, suggesting that the recovery process is not a mere reversal of ischemia-induced events. The observation that the entire population of CA 1 neurons in the anterior hippocampus die at 4 days of recirculation following 5 min of bilateral ischemia in the gerbil provides a reproducible response for investigating the biochemical events that precede cell death. The proposed experiments are designed to: 1) examine the effects of transient ischemia on long-term metabolic recovery in brain regions exhibiting different levels of susceptibility to ischemia, 2) test a number of current hypotheses concerning the pathomechanisms of ischemic cell death and delayed neuronal death and 3) further evaluate the neuroprotective effects of GABAergic agents. In these experiments in vivo, the levels of high-energy phosphates, glucose-related metabolites, cyclic nucleotides and certain amino acid neurotransmitters will be measured in the somal layer of the CA 1 and CA 3 region of the hippocampus and the cortex at various times of recirculation following 5 min of bilateral ischemia. The tissue samples weigh approximately 1 ug and microquantitative histochemical methods will be required to measure the metabolites in the pmole range. Finally, the loss of the CA 1 neurons at 4 days of reflow following 5 min of bilateral ischemia greatly increases the glia to neuron ratio in this region. This neuron-depleted area will be examined both during a secondary ischemia and recirculation to determine the contribution of a glial-enriched tissue to the ischemic response. A greater glial acidification during ischemia has been demonstrated, but the metabolic correlates in glia have not been examined. The importance of acid-base balance in glia may well explain the evolution of ischemic cell damage. The natural history of delayed neuronal death will be better described by these discrete measurements and it is anticipated that the information will serve as a temporal and biochemical guide for testing novel therapeutic approaches to the treatment of stroke.