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  • Title: Nonadditive neuroprotection with early glutamate receptor blockade and delayed hypothermia after asphyxia in preterm fetal sheep.
    Author: George SA, Barrett RD, Bennet L, Mathai S, Jensen EC, Gunn AJ.
    Journal: Stroke; 2012 Nov; 43(11):3114-7. PubMed ID: 22923445.
    Abstract:
    BACKGROUND AND PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: Early N-methyl-d-aspartate blockade and a clinical regime of delayed whole-body hypothermia provide nonadditive neuroprotection in the preterm brain.
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