Church J, Zeman S, Lodge D
Department of Physiology, Royal Veterinary College, London, United Kingdom.
Anesthesiology. 1988 Nov;69(5):702-9. doi: 10.1097/00000542-198811000-00011.
The neuroprotective activity of two systemically administered N-methyl-D-aspartate (NMDA) receptor antagonists, ketamine and MK-801, were investigated in a long-term recovery model of near-complete forebrain ischemia in the rat. Doses of each drug were chosen on the basis of the known degree and time course of NMDA antagonism seen in vivo after their systemic administration. Ketamine, administered at a dose of 20 mg.kg-1 iv, either immediately before or shortly after the 10-min ischemic period, failed to lessen neuronal damage in the selectively vulnerable hippocampal CA1 region. Increasing doses of ketamine administered over an increasing length of time in the postischemic period, however, did provide significant protection. MK-801 0.25 or 0.5 mg.kg-1 iv administered before ischemia also resulted in significant protection. The results support the proposal that NMDA receptor-mediated events may contribute to neuronal damage in selectively vulnerable regions of the central nervous system after ischemia.
在大鼠近乎完全性前脑缺血的长期恢复模型中，研究了两种全身给药的N-甲基-D-天冬氨酸（NMDA）受体拮抗剂氯胺酮和MK-801的神经保护活性。每种药物的剂量是根据其全身给药后在体内已知的NMDA拮抗程度和时间进程来选择的。在10分钟缺血期之前或之后不久静脉注射20mg.kg-1剂量的氯胺酮，未能减轻选择性易损海马CA1区的神经元损伤。然而，在缺血后时期，随着时间延长增加氯胺酮的剂量确实提供了显著的保护作用。在缺血前静脉注射0.25或0.5mg.kg-1剂量的MK-801也产生了显著的保护作用。这些结果支持了这样的观点，即NMDA受体介导的事件可能在缺血后中枢神经系统的选择性易损区域导致神经元损伤。
