Effects of tissue- and cellular-environments on the recovery of neuronal functions from cerebral ischemia

1)酸中毒被认为是缺血性神经元损伤的原因之一。而在轻度酸性条件下(pH 6.7-6.8)的大鼠海马片上，氧-糖剥夺引起的[Ca~(2+)]_i快速升高和快速去极化反应被减缓和延缓，而场电位在缺氧-糖剥夺10min后的恢复有所改善。结果表明，轻度酸中毒对海马神经元的缺血损伤具有保护作用。2)高K~+、藜芦碱和NMDA等去极化药物可引起CA1区锥体细胞层pH_i降低，[Ca~(2+)&gt；]_i升高。尽管在无钙介质中[Ca~(2+)]_i的升高几乎完全被抑制，但各pH_i酸移的主要部分保持不变。缺糖使高K~(++)和NMDA引起的pH_i酸移减少了三分之二。暴露于去极剂的切片中乳酸含量显著增加。结果表明，去极剂引起的pH_i酸移主要是由于乳酸加速糖酵解积累所致。依赖于钙离子的过程也可能在一定程度上导致pH_i酸移。由于[H^+]的增加降低了神经元的兴奋性，膜去极化促进的羟酵解酸的产生可能有助于防止神经元的过度兴奋。3)在短暂性前脑缺血4min后18~20h制备的沙土鼠海马片上，用一种潜在的敏感染料光学记录神经元兴奋性。当电刺激Schaffer络脉时，神经元兴奋在同一层内传播，并抑制向锥体层和东方层的顺向传播。因此，尽管没有发现锥体神经元变性，但神经元功能障碍可能在短暂性脑缺血18-20小时后就已经出现。

1) Acidosis is thought to be one of the causes of ischemic neuronal damage. However, in rat hippocampal slices under mildly acidotic conditions (pH 6.7-6.8), a characteristic rapid [Ca^<2+>]_i increase and rapid depolarization induced by oxygen-glucose deprivation were slowed and retarded, and recovery of field potential following 10 min of oxygen-glucose deprivation was improved. The results suggest that mild acidosis protects hippocampal neurons against ischemic damage.2) Depolarizing agents, including high K^+, veratridine and NMDA,elicited a decrease in pH_i and an elevation of [Ca^<2+>]_i in the CA1 pyramidal cell layr. Although the [Ca^<2+>]_i increase was almost completely suppressed in Ca^<2+> -free media, a major part of each pH_i acid shift remained unchanged. Glucouse-deprivation reduced pH_i acid shifts induced by both high K^+ and NMDA by two-third. Lactate contents significantly increased in slices exposed to the depolarizing agents. The results suggest that pH_i acid shifts produced by the depolarizing agents are mainly due to lactate accumulation by accelerated glycolysis. A Ca^<2+> -dependent process may also contribute in part to pH_i acid shifts. Since an increase in [H^+] decreases neuronal excitability, glycolytic acid production promoted by membrane depolarization may contribute to prevent excessive neuronal excitation. 3) Neuronal excitability was optically recorded in gerbil hippocampal slices, which was prepared 18-20 hr after transient forebrain ischemia for 4 min, using a potential sensitive dye. When Schaffer collaterals were electrically stimulated, neuronal excitation was spreaded within the same stratum and orthodromic spreading to strata pyramidale and oriens was inhibited. Thus, neuronal dysfunction might already occur 18-20 hr after the transient ischemia, although degeneration of pyramidal neurons was not found.