Hayakawa T, Hamada Y, Maihara T, Hattori H, Mikawa H
Department of Pediatrics, Faculty of Medicine, Kyoto University, Japan.
Life Sci. 1994;54(6):387-92. doi: 10.1016/0024-3205(94)00696-2.
We investigated the possible protective effect of phenytoin on hypoxic-ischemic brain damage in neonatal rats. Six-day-old rats underwent ligation of the left carotid artery followed by exposure to an 8% oxygen atmosphere for 2.5 hrs. We sacrificed the animals 72 hrs later and assessed the hypoxic-ischemic brain damage histologically. Phenytoin (50 mg/kg), administered intraperitoneally 1 hr before the hypoxia, reduced hypoxic-ischemic infarction in the cerebral cortex and striatum, and attenuated neuronal necrosis in the hippocampus. The plasma concentration of phenytoin after injection was 11.1 +/- 1.9 micrograms/ml (mean +/- S.E.M.) at 1 hr and 22.9 +/- 1.4 micrograms/ml at 4 hrs. Percent volumes of the infarction calculated by dividing the sum of damaged areas by the total area in serial coronal sections were 79 +/- 3% (mean +/- S.E.M.) in vehicle controls versus 13 +/- 6% in phenytoin-treated pups in the cerebral cortex, and 79 +/- 4% in vehicle controls versus 12 +/- 5% in phenytoin-treated pups in the striatum. We semiquantitatively investigated the hypoxic-ischemic change in 5 hippocampal areas: dentate gyrus, CA4, CA3, CA1, and subiculum, in the dorsal hippocampus. Pre-hypoxic treatment with phenytoin reduced hypoxic-ischemic damage in all areas examined. When phenytoin was administered immediately after the hypoxia, there was no difference between vehicle-injected controls and phenytoin-treated pups. These results demonstrate that phenytoin can reduce neonatal hypoxic-ischemic brain damage.
我们研究了苯妥英对新生大鼠缺氧缺血性脑损伤的可能保护作用。6日龄大鼠行左颈动脉结扎，随后置于8%氧气环境中2.5小时。72小时后处死动物，进行组织学评估缺氧缺血性脑损伤情况。在缺氧前1小时腹腔注射苯妥英（50mg/kg），可减少大脑皮质和纹状体的缺氧缺血性梗死，并减轻海马区神经元坏死。注射后1小时苯妥英的血浆浓度为11.1±1.9μg/ml（平均值±标准误），4小时时为22.9±1.4μg/ml。通过将连续冠状切片中损伤面积总和除以总面积计算得出的梗死体积百分比，在大脑皮质中，溶剂对照组为79±3%（平均值±标准误），苯妥英治疗组幼鼠为13±6%；在纹状体中，溶剂对照组为79±4%，苯妥英治疗组幼鼠为12±5%。我们对背侧海马的5个海马区：齿状回、CA4、CA3、CA1和下托进行了缺氧缺血性变化的半定量研究。缺氧前用苯妥英治疗可减少所有检测区域的缺氧缺血性损伤。在缺氧后立即给予苯妥英，注射溶剂的对照组和苯妥英治疗组幼鼠之间没有差异。这些结果表明苯妥英可减轻新生大鼠缺氧缺血性脑损伤。
