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Striatal neurons undergo prominent necrosis after HI. The mechanisms for this degeneration are not well understood. Postasphyxic hypothermia ameliorates the striatal necrosis, but the mechanisms of hypothermia\u2010induced neuroprotection are not known. We used a newborn piglet model of hypoxic\u2010asphyxic cardiac arrest to test the hypotheses that <jats:italic>N<\/jats:italic>\u2010methyl\u2010<jats:sc>d<\/jats:sc>\u2010aspartate receptor activation and free radical damage coexist, prior to neurodegeneration, early after resuscitation, and that these changes are attenuated with hypothermia. Piglets were subjected to 30 min of hypoxia followed by 7 min of airway occlusion, causing asphyxic cardiac arrest, and then were resuscitated and survived normothermically for 5 min, 3 h, or 6 h, or hypothermically for 3 h. By 6 h of normothermic recovery, 50% of neurons in putamen showed ischemic cytopathology. Striatal tissue was fractionated into membrane or soluble proteins and was assayed by immunoblotting for carbonyl modification, phosphorylation of the <jats:italic>N<\/jats:italic>\u2010methyl\u2010<jats:sc>d<\/jats:sc>\u2010aspartate receptor subunit NR1, and neuronal nitric oxide synthase. Significant accumulation of soluble protein carbonyls was present at 3 h (196% of control) and 6 h (142% of control). Phosphorylation of serine\u2010897 of NR1 was increased significantly at 5 min (161% of control) and 3 h (226% of control) after HI. Phosphorylation of serine\u2010890 of NR1 was also increased after HI. Membrane\u2010associated neuronal nitric oxide synthase was increased by 35% at 5 min. Hypothermia attenuated the oxidative damage and the NR1 phosphorylation in striatum. We conclude that neuronal death signaling in newborn striatum after HI is engaged rapidly through <jats:italic>N<\/jats:italic>\u2010methyl\u2010<jats:sc>d<\/jats:sc>\u2010aspartate receptor activation, neuronal nitric oxide synthase recruitment, and oxidative stress. Postasphyxic, mild whole body hypothermia provides neuroprotection by suppressing <jats:italic>N<\/jats:italic>\u2010methyl\u2010<jats:sc>d<\/jats:sc>\u2010aspartate receptor phosphorylation and protein oxidation.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.ijdevneu.2007.08.015","type":"journal-article","created":{"date-parts":[[2007,9,11]],"date-time":"2007-09-11T11:08:46Z","timestamp":1189508926000},"page":"67-76","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Rapid NMDA receptor phosphorylation and oxidative stress precede striatal neurodegeneration after hypoxic ischemia in newborn piglets and are attenuated with hypothermia"],"prefix":"10.1002","volume":"26","author":[{"given":"Dawn","family":"Mueller\u2010Burke","sequence":"first","affiliation":[{"name":"School of Nursing, University of Maryland at Baltimore Baltimore MD 21201 United States"},{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore MD 21205 United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond C.","family":"Koehler","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore MD 21205 United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee J.","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins University School of Medicine Baltimore MD 21205 United States"},{"name":"Department of Neuroscience Johns Hopkins University School of Medicine Baltimore MD 21205 United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,9,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000072783.22373.FF"},{"key":"e_1_2_7_3_1","first-page":"1786","article-title":"Proton spectroscopy and diffusion imaging on the first day of life after perinatal asphyxia: preliminary report","volume":"22","author":"Barkovich A.J.","year":"2001","journal-title":"Am. 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