Department of Physiology, The University of Auckland, Private Bag 92019, Auckland 1023, New Zealand.
Stroke. 2012 Nov;43(11):3114-7. doi: 10.1161/STROKEAHA.112.671982. Epub 2012 Aug 23.
Hypothermia induced after perinatal hypoxia-ischemia is partially protective. This study examined whether early treatment with the noncompetitive N-methyl-d-aspartate receptor antagonist, dizocilpine, can augment neuroprotection with delayed hypothermia after severe asphyxia in preterm fetal sheep at 0.7 weeks gestation (equivalent to 28-32 weeks in humans).
Fifty minutes after umbilical cord occlusion for 25 minutes, fetuses were randomized to either dizocilpine (2 mg/kg estimated fetal weight intravenously, then 0.07 mg/kg/h for 4 hours) and then after 5.5 hours to whole-body cooling to 3°C below baseline, or sham cooling, until 72 hours, and euthanized 7 days after umbilical cord occlusion.
Delayed hypothermia was associated with improved neuronal survival (P<0.02) and reduced microglia (P=0.004) and caspase-3-positive cells (P<0.01) compared with umbilical cord occlusion. Dizocilpine was associated with reduced microglia (P<0.05) but no effect on caspase-3 induction and improved survival only in CA1/2 (P<0.05) with no apparent additive effect with delayed hypothermia.
Early N-methyl-d-aspartate blockade and a clinical regime of delayed whole-body hypothermia provide nonadditive neuroprotection in the preterm brain.
围产期缺氧缺血后诱导的低温具有部分保护作用。本研究旨在探讨在妊娠 0.7 周（相当于人类 28-32 周）的早产胎儿羊中，严重窒息后延迟使用非竞争性 N-甲基-D-天冬氨酸受体拮抗剂地佐西平是否可以增强低温的神经保护作用。
脐带结扎 25 分钟后 50 分钟，将胎儿随机分为地佐西平（2 mg/kg 估计胎儿体重静脉注射，然后 0.07 mg/kg/h 持续 4 小时）组和假冷却组，然后在 5.5 小时后进行全身冷却至基础体温以下 3°C，直至 72 小时，并在脐带结扎后 7 天处死。
与脐带结扎相比，延迟低温可改善神经元存活（P<0.02）和减少小胶质细胞（P=0.004）和 caspase-3 阳性细胞（P<0.01）。地佐西平与小胶质细胞减少有关（P<0.05），但对 caspase-3 诱导无影响，仅在 CA1/2 区改善存活（P<0.05），与延迟低温无明显相加作用。
早期 N-甲基-D-天冬氨酸阻断和延迟全身低温的临床方案在早产儿脑提供非相加的神经保护作用。
