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。而在轻度酸中毒（pH 6.7-6.8）条件下，缺氧缺糖引起的海马脑片[Ca^<2+>] i快速升高和快速去极化现象被减缓和延迟，缺氧缺糖10 min后的场电位恢复得到改善。2）去极化剂包括高K^+、藜芦碱和NMDA可引起海马CA 1区锥体细胞层pH_i降低和[Ca^<2+>]_i升高。虽然在无Ca^<2 +>的培养基中[Ca^<2 +>]_i的增加几乎被完全抑制，但每个pH_i酸位移的大部分保持不变。葡萄糖剥夺使高K^+和NMDA诱导的pH_i酸位移降低了三分之二。乳酸含量显着增加切片暴露于去极化剂。结果表明，去极化剂引起的pH_i酸位移主要是由于糖酵解加速导致乳酸积累所致。Ca^<2+>依赖性过程也可能对pH_i酸位移有部分贡献.由于[H^+]的增加降低了神经元的兴奋性，因此膜去极化促进的糖酵解酸的产生可能有助于防止神经元过度兴奋。3)在短暂前脑缺血4分钟后18-20小时制备的沙鼠海马切片中，使用电位敏感染料光学记录神经元兴奋性。当电刺激Schaffer侧支时，神经元兴奋在同一层内传播，向皮层和起源层的顺向传播受到抑制。因此，神经元功能障碍可能已经发生后18-20小时短暂缺血，虽然没有发现锥体神经元的变性。

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.