Gusev E I, Skvortsova V I
Russian State Medical University, Moscow.
Usp Fiziol Nauk. 2002 Oct-Dec;33(4):80-93.
This article is dedicated to the mechanisms of ischaemic brain damage. The processes of glutamate-calcium cascade connected with formation of focal brain necrosis within the period of therapeutic window (the first 3-6 h after the induction of cerebral ischaemia) are discussed. The basis mechanisms of energy-dependent ionic pumps failure, development of glutamate excitotoxicity, disorders of calcium metabolism are analyzed. The results of own investigations are presented. The significant increases in the concentrations of excitatory aminoacidergic neurotransmitters (glutamate and aspartate) in the cerebrospinal fluid were demonstrated in patients with acute ischaemic strokes from the first hours of illness with no dependency on vascular origin of strokes. The extent and duration of these increases were of prognostic value for determining the severity and outcome of the stroke. It was showed that along with "excitotoxicity", the pathogenesis of ischaemic stroke also involves a deficiency of protective inhibitory GABAergic mechanisms and developing imbalance between the excitatory and inhibitory neurotransmitters systems. The significant increase of the level of the specific autoantibodies to phencyclidine-binding protein of glutamate NMDA-receptors was found out in blood serum of patients beginning from the first 3 h after stroke onset and it directly correlated with the severity of ischaemic stroke. The great attention is paid to the role of astroglia in energy metabolism and glutamate neurotransmission, to the mechanisms of regulation of concentrations of neurotransmitter amino acids in the synaptic cleft, as well as to the mechanisms of spreading depression waves and zinc neurotoxicity.
本文致力于探讨缺血性脑损伤的机制。文中讨论了在治疗窗内(脑缺血诱导后的最初3 - 6小时)与局灶性脑坏死形成相关的谷氨酸 - 钙级联反应过程。分析了能量依赖性离子泵功能衰竭、谷氨酸兴奋性毒性发展以及钙代谢紊乱的基本机制。展示了自身研究的结果。急性缺血性卒中患者在发病后的最初数小时内,脑脊液中兴奋性氨基酸能神经递质(谷氨酸和天冬氨酸)浓度显著升高,且与卒中的血管起源无关。这些升高的程度和持续时间对于确定卒中的严重程度和预后具有预后价值。研究表明,除了“兴奋性毒性”外,缺血性卒中的发病机制还涉及保护性抑制性γ-氨基丁酸能机制的缺乏以及兴奋性和抑制性神经递质系统之间逐渐发展的失衡。从卒中发作后的最初3小时起,在患者血清中发现谷氨酸N-甲基-D-天冬氨酸受体苯环利定结合蛋白的特异性自身抗体水平显著升高,且与缺血性卒中的严重程度直接相关。文中还高度关注了星形胶质细胞在能量代谢和谷氨酸神经传递中的作用、突触间隙中神经递质氨基酸浓度的调节机制以及扩散性抑制波和锌神经毒性的机制。