Gunn A J, Mydlar T, Bennet L, Faull R L, Gorter S, Cook C, Johnston B M, Gluckman P D
Department of Paediatrics, University of Auckland, New Zealand.
Pediatr Res. 1989 Jun;25(6):573-6. doi: 10.1203/00006450-198906000-00003.
One postulated final common pathway leading to neuronal death after hypoxic-ischemic insults is an increase in intracellular calcium concentrations. We examined the effect of pretreatment with flunarizine, a calcium channel antagonist known to pass the blood brain barrier, on the behavioral and histologic changes after an hypoxic-ischemic insult in the infant rat. The 21-d-old rats were subjected to unilateral carotid ligation, then to 2 h of hypoxia. They were pretreated with either flunarizine (30 mg/kg, intraperitoneally) or with an equal volume of diluent. After 5 days of observation they were killed for histology. Acute behavioral abnormalities were observed in more controls than treatment animals, 52 vs 11% (p less than 0.002). Cerebral injury was almost entirely confined to the ligated side and was significantly worse in the control rats. Full thickness cortical infarction was noted in 56% of controls (n = 27) vs 4% of flunarizine-treated rats (n = 24), (p less than 0.001). Mean and maximum damage scores for all areas assessed including cortex, corpus striatum, thalamus, amygdala, and hippocampus were improved markedly in treatment rats (p less than 0.005). These observations confirm that flunarizine, when given prophylactically, has a neuroprotective effect against hypoxic-ischemic injury in the developing brain.
一种假定的缺氧缺血性损伤后导致神经元死亡的最终共同途径是细胞内钙浓度增加。我们研究了氟桂利嗪（一种已知可通过血脑屏障的钙通道拮抗剂）预处理对幼鼠缺氧缺血性损伤后行为和组织学变化的影响。21日龄大鼠接受单侧颈动脉结扎，然后缺氧2小时。它们分别用氟桂利嗪（30mg/kg，腹腔注射）或等体积的稀释剂进行预处理。观察5天后，将它们处死进行组织学检查。观察到急性行为异常的对照组动物比治疗组动物多，分别为52%和11%（p<0.002）。脑损伤几乎完全局限于结扎侧，且对照组大鼠的损伤明显更严重。56%的对照组（n=27）出现全层皮质梗死，而氟桂利嗪治疗组大鼠为4%（n=24），（p<0.001）。治疗组大鼠包括皮质、纹状体、丘脑、杏仁核和海马体在内的所有评估区域的平均损伤评分和最大损伤评分均有显著改善（p<0.005）。这些观察结果证实，预防性给予氟桂利嗪对发育中的大脑缺氧缺血性损伤具有神经保护作用。
