Andiné P, Orwar O, Jacobson I, Sandberg M, Hagberg H
Institute of Neurobiology, University of Göteborg, Sweden.
J Neurochem. 1991 Jul;57(1):230-6. doi: 10.1111/j.1471-4159.1991.tb02120.x.
An excessive activation of the excitatory amino acid system has been proposed as one possible mediator of the ischemia-induced delayed death of CA1 pyramidal cells in the hippocampus. Using dialytrodes in the CA1 of the rat, we have investigated multiple-unit activity and extracellular changes in acidic sulfur-containing amino acids and gamma-glutamyl peptides during ischemia (20-min, four-vessel occlusion) and during 8 h of reflow. Multiple-unit activity was abolished during ischemia and for the following 1 h, but then recovered, gradually reaching preischemic levels after 8 h of reflow. Extracellular cysteate, cysteine sulfinate, and gamma-glutamyltaurine increased (1.5- to threefold) during ischemia, and extracellular glutathione and gamma-glutamylaspartate plus gamma-glutamylglutamine increased during early reflow (two- to threefold). The recovery of neuronal activity at 4-8 h was paralleled by an increase in extracellular cysteine sulfinate (2.5-fold at 8 h of reflow). Perfusion with 10 microM tetrodotoxin at 8 h of reflow abolished the multiple-unit activity and reduced extracellular cysteine sulfinate. Considering the glutamate-like properties of cysteine sulfinate, the observed postischemic increase may be involved in the development of the delayed neuronal death.
兴奋性氨基酸系统的过度激活被认为是海马CA1区锥体细胞缺血诱导延迟死亡的一种可能介质。利用大鼠CA1区的透析电极，我们研究了缺血（20分钟，四动脉闭塞）及8小时再灌注期间多单位活动以及含酸性硫氨基酸和γ-谷氨酰肽的细胞外变化。缺血期间及随后1小时多单位活动消失，但随后恢复，再灌注8小时后逐渐达到缺血前水平。缺血期间细胞外半胱亚磺酸、半胱氨酸亚磺酸盐和γ-谷氨酰牛磺酸增加（1.5至3倍），早期再灌注期间细胞外谷胱甘肽以及γ-谷氨酰天冬氨酸加γ-谷氨酰谷氨酰胺增加（2至3倍）。4至8小时神经元活动的恢复与细胞外半胱氨酸亚磺酸盐的增加平行（再灌注8小时时增加2.5倍）。再灌注8小时时用10微摩尔河豚毒素灌注可消除多单位活动并降低细胞外半胱氨酸亚磺酸盐。考虑到半胱氨酸亚磺酸盐类似谷氨酸的特性，观察到的缺血后增加可能与延迟性神经元死亡的发生有关。
