Meldrum B
Department of Neurology, Institute of Psychiatry, London, United Kingdom.
Cerebrovasc Brain Metab Rev. 1990 Spring;2(1):27-57.
An excitotoxic action of glutamate and aspartate contributes to the pathological outcome after transient global cerebral ischaemia, focal ischaemia, neonatal hypoxia/ischaemia, and secondary ischaemia following brain trauma. This provides a therapeutic approach utilising drugs acting on (i) glutamate release, (ii) postsynaptic glutamate receptors, and (iii) the secondary events following receptor activation (including the arachidonic acid cascade). Both NMDA and non-NMDA receptors are involved in the excitotoxic effects of glutamate and aspartate. The availability of competitive and noncompetitive antagonists acting at the NMDA receptor has permitted the demonstration of cerebroprotective effects of these compounds in animal models of global, focal, neonatal, and secondary cerebral ischaemia. Protection is seen with antagonist administration prior to and after the onset of ischaemia. The postischaemic therapeutic time window is not fully defined for the different models but is in the range of 0-20 min for incomplete global ischaemia and 1-3 h for focal ischaemia. The clinical usefulness of this approach remains to be established.
谷氨酸和天冬氨酸的兴奋毒性作用在短暂性全脑缺血、局灶性缺血、新生儿缺氧/缺血以及脑外伤后继发性缺血后的病理转归中发挥作用。这提供了一种治疗方法，即利用作用于以下方面的药物：（i）谷氨酸释放；（ii）突触后谷氨酸受体；（iii）受体激活后的继发性事件（包括花生四烯酸级联反应）。NMDA受体和非NMDA受体均参与谷氨酸和天冬氨酸的兴奋毒性作用。作用于NMDA受体的竞争性和非竞争性拮抗剂的出现，使得在全脑、局灶性、新生儿和继发性脑缺血的动物模型中证实了这些化合物的脑保护作用。在缺血发作之前和之后给予拮抗剂均可观察到保护作用。对于不同模型，缺血后治疗时间窗尚未完全明确，但对于不完全性全脑缺血为0 - 20分钟，对于局灶性缺血为1 - 3小时。这种方法的临床实用性仍有待确定。
