Temporal ordering of pathogenic events following transient global ischemia
Temporal ordering of pathogenic events following transient global ischemia
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DOI：
10.1016/s0006-8993(97)01414-5
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发表时间：
1998-04-20
期刊：
影响因子：
2.9
通讯作者：
Lynch, G
中科院分区：
文献类型：
--
作者：
Bartus, RT;Dean, RL;Lynch, G
使大鼠遭受短暂性整体缺血（四血管闭塞），并表征选择性易损海马区 CA1 中与时间相关的变化。评估包括对传入刺激、银染色、钙蛋白酶诱导的血影蛋白分解、色谱溶解和细胞死亡的离体场反应，从缺血后 6 小时开始，一直持续到几天后发生锥体细胞完全崩解。观察到的最早的变化是场 CAI 电位的斜率和振幅适度增加（6 小时）。高反应性在较高刺激电流下最为明显，并且在缺血后 16 小时持续保持不变。缺血后 24 小时内可检测到三种效应：(a) 钙蛋白酶介导的血影蛋白分解产物浓度增加； (b) CA1 区深部锥体神经元的银染色增强，放射层染色较少，但仍然明显，(c) CA1 区对传入刺激的反应幅度和斜率降低。血影蛋白分解产物的浓度和银染色的强度均在缺血后四天逐渐增加至最大值，而场响应的幅度和斜率在24至48小时之间下降至非常低的水平。尼氏染色的干扰最终在 48 小时时变得明显，在缺血后五天染色几乎完全消失。这项研究首次证明了钙蛋白酶蛋白水解、锥体细胞的亚细胞损伤及其在整体缺血后最终死亡之前的功能丧失之间存在密切的早期时间关系。 (C) 1998 Elsevier Science B.V.
Rats were subjected to transient global ischemia (four vessel occlusion) and time-related changes in the selectively vulnerable hippocampal field CA1 were characterized. The assessment included ex vivo field responses to afferent stimulation, silver staining, calpain-induced spectrin breakdown, chromatolysis, and cell death, beginning at 6 h post-ischemia and continuing until total disintegration of the pyramidal cells occurred several days later. The earliest change observed was a modest increase in the slope and amplitude of field CAI potentials (at 6 h). The hyperresponsiveness was most apparent at higher stimulation currents and persisted unchanged at 16 h post-ischemia. Three effects became detectable within 24 h, post-ischemia: (a) an increase in concentrations of calpain-mediated, spectrin breakdown products; (b) enhanced silver staining in the deep pyramidal neurons of the field CA1 with lesser, though still apparent, staining of stratum radiatum, and (c) a decrease in amplitude and slope of field CA1 responses to afferent stimulation. Both the concentration of spectrin breakdown products and the intensity of silver staining progressively increased to a maximum at four days post ischemia, while the amplitude and slope of the field responses dropped to a very low level between 24 and 48 h. Disturbances of Nissl staining were finally evident at 48 h, with nearly complete disappearance of staining at five days post-ischemia. This study provides the first demonstration of a close and early temporal relationship between calpain proteolysis, subcellular damage to the pyramidal cells and their loss of function following global ischemia, prior to their eventual death. (C) 1998 Elsevier Science B.V.