Dogan A, Eras M A, Rao V L, Dempsey R J
Department of Neurological Surgery, University of Wisconsin and Veterans Administration Hospital, Madison, WI 53792, USA.
Acta Neurochir (Wien). 1999;141(10):1107-13. doi: 10.1007/s007010050491.
Memantine, an uncompetitive NMDA open-channel blocker, has been shown to be effective in preventing neuronal damage after permanent focal cerebral ischemia. Reperfusion after a long period of ischemia may aggravate the progression of neuronal damage. Those drugs that show protective effects after permanent cerebral ischemia, therefore, might fail to do so against ischemia-reperfusion injury. In this study we evaluated the effects of memantine on brain edema formation and ischemic injury volume after transient cerebral ischemia. Male Spontaneously Hypertensive Rats (SHR) weighing 250-300 g were anesthetized with halothane and subjected to 1 hour of temporary middle cerebral artery occlusion by an intraluminal suture. 20 mg/kg of memantine or saline were injected intraperitoneally 5 min. after the induction of ischemia. Physiological parameters and regional cerebral blood flow were monitored during the surgical procedure. Brain water content and ischemic injury volume were measured with the wet dry method and 2,3,5-triphenyl tetrazolium chloride monohydrate (TTC) staining, respectively, at 24 hours after occlusion. There were no statistically significant differences between the groups regarding physiological parameters during the procedure. Memantine treatment (n=9) reduced the brain water content significantly in the cortex compared to saline treatment (n=8; 83. 1+/-0.7% vs. 84.5+/-1.5%, respectively, p<0.05). The total volume of ischemic brain injury was 300+/-49 mm(3) in the animals treated with saline (n=13). Treatment with 20 mg/kg memantine (n=14) reduced the ischemic injury volume to 233+/-61 mm(3) (P<0.01). These results demonstrate that the harmful effects of recirculation after a period of ischemia can be attenuated by the treatment of memantine, perhaps by its action at the NMDA receptors.
美金刚是一种非竞争性N-甲基-D-天冬氨酸（NMDA）开放通道阻滞剂，已被证明在预防永久性局灶性脑缺血后神经元损伤方面有效。长时间缺血后的再灌注可能会加重神经元损伤的进展。因此，那些在永久性脑缺血后显示出保护作用的药物，可能对缺血再灌注损伤无效。在本研究中，我们评估了美金刚对短暂性脑缺血后脑水肿形成和缺血损伤体积的影响。体重250 - 300克的雄性自发性高血压大鼠（SHR）用氟烷麻醉，通过腔内缝合线进行1小时的大脑中动脉临时闭塞。缺血诱导后5分钟，腹腔注射20毫克/千克美金刚或生理盐水。手术过程中监测生理参数和局部脑血流量。闭塞后24小时，分别用干湿法和2,3,5 - 氯化三苯基四氮唑（TTC）染色测量脑含水量和缺血损伤体积。两组在手术过程中的生理参数无统计学显著差异。与生理盐水治疗组（n = 8）相比，美金刚治疗组（n = 9）显著降低了皮质中的脑含水量（分别为83.1±0.7%和84.5±1.5%，p < 0.05）。生理盐水治疗的动物（n = 13）缺血性脑损伤的总体积为300±49立方毫米。用20毫克/千克美金刚治疗（n = 14）使缺血损伤体积减少至233±61立方毫米（P < 0.01）。这些结果表明，美金刚治疗可能通过其对NMDA受体的作用减轻缺血一段时间后再灌注的有害影响。
