Pathophysiology and treatments of brain ischemia insighted from neuronal function, metabolism and molecular structure

(1)损伤后1-3天，机械损伤海马切片中[Ca^<2+>] _i在缺氧-葡萄糖剥夺下的升高受到抑制。这一事实表明，内在的抗缺血活动可能在损伤附近被诱导。(2)氧-葡萄糖剥夺引起的膜电位快速去极化后，1 ~ 1.5 min内可产生不可逆的神经元变化。Ca^<2+>-通过NMDA受体通道内流和Ca^<2+>从细胞内释放可能与不可逆的神经元变化有关。(3)轻度酸中毒可抑制氧-葡萄糖剥夺时海马神经元[Ca^<2+>] _i的升高和膜去极化。(4)神经胶质细胞中[Ca^<2+>] _i的活跃变化表明神经胶质在诱导神经元LTP和缺血变化中起重要作用。(5)海马苔藓纤维- ca3突触LTP可能是突触前诱导的。(6)参与海马化学递质释放的电压门控钙通道属于p型和l型高阈值钙通道，而不属于n型钙通道。(7)确定了组成NMDA受体亚型的分子结构。各亚型的不同分布可能与神经元对缺血性损伤的易感性有关。(8)测定与突触前膜释放神经递质相关的钙结合蛋白。这些蛋白可能与受体介导的细胞内信号转导有关。(9)为评估缺血诱导的未知基因家族，提出了一种新的、高灵敏度的cDNA减法“定向标签PCR减法”。（10）一氧化氮合酶抑制剂减少梗死面积。花生四烯酸代谢抑制剂抑制海马切片不可逆神经元去极化。

(1)Increase in [Ca^<2+>] _i in response to oxygen-glucose deprivation was inhibited in mechanically injured hippocampal slices in comparison with non-injured slices 1-3 days after the injury. The fact suggests that intrinsic anti-ischemic activity may be induced in the vicinity of the injury. (2)Irreversible neuronal changes may be produced at 1-1.5 minfollowing a rapid depolarization of membrane potential induced by oxygen-glucose deprivation. Both Ca^<2+>-influx through NMDA receptor channels and Ca^<2+>release from intracellular site may associate the irreversible neuronal changes. (3) Mild acidosis inhibited both of increases in [Ca^<2+>] _i and membrane depolarization of hippocampal neurons in response to oxygen-glucose deprivation. (4)Active changes in [Ca^<2+>] _i in glial cells indicate important roles of glia for induction of LTP and ischemic changes in neurons.(5)LTP in hippocampal mossy fiber-CA3 synaps was suggested to be induced presynaptically. (6)Voltage-gated calcium channels contributing to release of chemical transmitters in hippocampus are assigned to be P-and L-type high threshold calcium channels but not to N-type calcium channels. (7)The molecular structure of subtypes composing the NMDA receptors was determined. Different distributions of each subtype may relate to vulnerability of neurons to ischemic damage. (8)Calcium binding proteins associating with neurotransmitter release from presynaptic membrane were determined. These proteins may associate with receptor-mediated intracellular signal transductions. (9)To assess unknown gene family induced by ischemia, new and high-sensitive cDNA subtraction method "directional tag PCR subtraction" was developed. (10)Nitric oxide synthase inhibitor reduced the infarction area. Inhibitors of the arachidonic acid metabolism inhibited the irreversible neuronal depolarization in hippocampal slices.