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.
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.
Authors: Junchao Zhu; Bing Wang; Jeong-Hoo Lee; Jillian S Armstrong; Ewa Kulikowicz; Utpal S Bhalala; Lee J Martin; Raymond C Koehler; Zeng-Jin Yang Journal: Dev Neurosci Date: 2015-02-25 Impact factor: 2.984
Authors: Joanne O Davidson; Alexandra L Rout; Guido Wassink; Caroline A Yuill; Frank G Zhang; Colin R Green; Laura Bennet; Alistair J Gunn Journal: J Cereb Blood Flow Metab Date: 2015-07-15 Impact factor: 6.200
Authors: Evelyn McClendon; Kevin Chen; Xi Gong; Elica Sharifnia; Matthew Hagen; Victor Cai; Daniel C Shaver; Art Riddle; Justin M Dean; Alistair J Gunn; Claudia Mohr; Joshua S Kaplan; David J Rossi; Christopher D Kroenke; A Roger Hohimer; Stephen A Back Journal: Ann Neurol Date: 2014-03-13 Impact factor: 10.422
Authors: Miriam E Koome; Joanne O Davidson; Paul P Drury; Sam Mathai; Lindsea C Booth; Alistair Jan Gunn; Laura Bennet Journal: PLoS One Date: 2013-10-18 Impact factor: 3.240
Authors: Joanne O Davidson; Guido Wassink; Lotte G van den Heuij; Laura Bennet; Alistair J Gunn Journal: Front Neurol Date: 2015-09-14 Impact factor: 4.003