Başkaya M K, Rao A M, Donaldson D, Prasad M R, Dempsey R J
Department of Neurological Surgery, University of Wisconsin Clinical Science Center, Madison, USA.
Neurosurgery. 1997 Feb;40(2):364-70; discussion 370-1. doi: 10.1097/00006123-199702000-00026.
Ifenprodil, a polyamine site N-methyl-D-aspartate receptor/channel antagonist, has been reported to decrease infarction volume after cerebral ischemia. However, the possible mechanisms of this protective effect have not been studied in detail. We investigated the effects of ifenprodil on ischemic injury size, blood-brain barrier (BBB) permeability, regional brain edema, and cerebral blood flow.
Focal ischemia for 6 hours was produced by permanent occlusion of the middle cerebral artery in 15 anesthetized cats. Treatment with drug (n = 8) or vehicle (n = 7) was initiated at 5 minutes after ischemia and continued for 3 hours. Physiological variables were continuously monitored during experiments. We measured ischemic injury size, brain edema, and BBB permeability to Evans blue and determined regional cerebral blood flow by using laser doppler flowmetry.
Both ischemic injury size and BBB permeability were smaller in the ifenprodil-treated group, compared with the saline-treated group (P < 0.05). Ifenprodil treatment also attenuated brain edema formation in the dense ischemic region, compared with saline treatment (1.035 +/- 0.002 versus 1.028 +/- 0.002, P < 0.05). There was no significant change in cerebral blood flow with ifenprodil treatment.
Findings from this study confirm that ifenprodil treatment results in a significant decrease in the size of ischemic injury after focal ischemia. The tissue-sparing effect of ifenprodil is not related to its vasoactive properties. It is likely that its neuroprotective effects are related to its ability to antagonize N-methyl-D-aspartate receptors, which results in a decrease in brain edema and BBB permeability.
已报道多胺位点N-甲基-D-天冬氨酸受体/通道拮抗剂艾芬地尔可减小脑缺血后的梗死体积。然而，这种保护作用的可能机制尚未得到详细研究。我们研究了艾芬地尔对缺血性损伤大小、血脑屏障（BBB）通透性、局部脑水肿和脑血流量的影响。
通过永久性闭塞15只麻醉猫的大脑中动脉造成6小时的局灶性缺血。在缺血后5分钟开始用药物（n = 8）或赋形剂（n = 7）治疗，并持续3小时。实验过程中持续监测生理变量。我们测量了缺血性损伤大小、脑水肿以及BBB对伊文思蓝的通透性，并使用激光多普勒血流仪测定局部脑血流量。
与生理盐水治疗组相比，艾芬地尔治疗组的缺血性损伤大小和BBB通透性均较小（P < 0.05）。与生理盐水治疗相比，艾芬地尔治疗还减轻了密集缺血区域的脑水肿形成（1.035±0.002对1.028±0.002，P < 0.05）。艾芬地尔治疗后脑血流量无显著变化。
本研究结果证实，艾芬地尔治疗可使局灶性缺血后缺血性损伤的大小显著减小。艾芬地尔的组织保护作用与其血管活性特性无关。其神经保护作用可能与其拮抗N-甲基-D-天冬氨酸受体的能力有关，这导致脑水肿和BBB通透性降低。
