Dirnagl U, Tanabe J, Pulsinelli W
Cerebrovascular Disease Research Center, Cornell University Medical College, New York, NY 10021.
Brain Res. 1990 Sep 10;527(1):62-8. doi: 10.1016/0006-8993(90)91060-t.
The effect of treatment with the potent, non-competitive NMDA receptor-channel antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a, d] cyclohepten-5,10-imine maleate (MK-801) on ischemia-induced brain damage was studied in a well-characterized model of focal neocortical infarction in spontaneously hypertensive rats. Anesthesia exposure was minimized to the surgical procedure and the infarcts were allowed to mature over a 24-h period. Pretreatment with 5 mg/kg i.p. MK-801 (n = 11 control, n = 12 treated animals) 30 min before induction of focal cerebral ischemia had no statistically significant influence on infarct volumes. However, pre- and post-treatment with MK-801 5 mg/kg i.p. 30 min before induction of ischemia and 2.5 mg/kg each at 8 and 16 h after onset of ischemia, reduced infarct volumes in two separate studies by 29% (investigator J.T., n = 5 control and n = 7 treated animals) and 20% (investigator U.D., n = 8 control and n = 8 treated animals), respectively. The combined reduction in infarct volume in MK-801-treated animals for both investigators was 23% (P = 0.016, ANOVA). The findings indicate a smaller neuroprotective effect of MK-801 in spontaneously hypertensive rats subjected to focal ischemia than in previous reports using normotensive animals.
在一个特征明确的自发性高血压大鼠局灶性新皮质梗死模型中，研究了强效非竞争性N-甲基-D-天冬氨酸（NMDA）受体通道拮抗剂（+）-5-甲基-10,11-二氢-5H-二苯并[a,d]环庚烯-5,10-亚胺马来酸盐（MK-801）治疗对缺血性脑损伤的影响。将麻醉暴露时间减至最短，仅用于手术过程，并使梗死灶在24小时内成熟。在局灶性脑缺血诱导前30分钟腹腔注射5mg/kg MK-801（n = 11只对照动物，n = 12只治疗动物），对梗死体积没有统计学上的显著影响。然而，在两项独立研究中，分别在缺血诱导前30分钟腹腔注射5mg/kg MK-801，以及在缺血发作后8小时和16小时各腹腔注射2.5mg/kg MK-801进行预处理和后处理，梗死体积分别减少了29%（研究者J.T.，n = 5只对照动物，n = 7只治疗动物）和20%（研究者U.D.，n = 8只对照动物，n = 8只治疗动物）。两位研究者的MK-801治疗动物的梗死体积综合减少了23%（P = 0.016，方差分析）。研究结果表明，与之前使用正常血压动物的报告相比，MK-801对自发性高血压大鼠局灶性缺血的神经保护作用较小。
