{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T05:24:21Z","timestamp":1735881861306,"version":"3.32.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,11]]},"abstract":"Abstract<\/jats:title>\n \n Background:<\/jats:title>\n Mild brain hypothermia (32\u00b0\u201334\u00b0C) after human neonatal asphyxia improves neurodevelopmental outcomes. Astrocytes but not neurons have pyruvate carboxylase and an acetate uptake transporter. 13<\/jats:sup>C nuclear magnetic resonance spectroscopy of rodent brain extracts after administering [1-13<\/jats:sup>C]glucose and [1,2-13<\/jats:sup>C]acetate can distinguish metabolic differences between glia and neurons, and tricarboxylic acid cycle entry via<\/jats:italic> pyruvate dehydrogenase and pyruvate carboxylase.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n Neonatal rat cerebrocortical slices receiving a 13<\/jats:sup>C-acetate\/glucose mixture underwent a 45-min asphyxia simulation via<\/jats:italic> oxygen\u2013glucose-deprivation followed by 6\u2009h of recovery. Protocols in three groups of N = 3 experiments were identical except for temperature management. The three temperature groups were: normothermia (37\u00b0C), hypothermia (32\u00b0C for 3.75\u2009h beginning at oxygen\u2013-glucose deprivation start), and delayed hypothermia (32\u00b0C for 3.75\u2009h, beginning 15\u2009min after oxygen\u2013glucose deprivation start). Multivariate analysis of nuclear magnetic resonance metabolite quantifications included principal component analyses and the L1-penalized regularized regression algorithm known as the least absolute shrinkage and selection operator<\/jats:italic>.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n The most significant metabolite difference (P<\/jats:italic> < 0.0056) was [2-13<\/jats:sup>C]glutamine\u2019s higher final\/control ratio for the hypothermia group (1.75\u2009\u00b1\u20090.12) compared with ratios for the delayed (1.12\u2009\u00b1\u20090.12) and normothermia group (0.94\u2009\u00b1\u20090.06), implying a higher pyruvate carboxylase\/pyruvate dehydrogenase ratio for glutamine formation. Least Absolute Shrinkage and Selection Operator found the most important metabolites associated with adenosine triphosphate preservation: [3,4-13<\/jats:sup>C]glutamate\u2014produced via<\/jats:italic> pyruvate dehydrogenase entry, [2-13<\/jats:sup>C]taurine\u2014an important osmolyte and antioxidant, and phosphocreatine. Final principal component analyses scores plots suggested separate cluster formation for the hypothermia group, but with insufficient data for statistical significance.<\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n Starting mild hypothermia simultaneously with oxygen\u2013glucose deprivation, compared with delayed starting or no hypothermia, has higher pyruvate carboxylase throughput, suggesting that better glial integrity is one important neuroprotection mechanism of earlier hypothermia.<\/jats:p>\n <\/jats:sec>","DOI":"10.1097\/aln.0b013e31829c2d90","type":"journal-article","created":{"date-parts":[[2013,6,7]],"date-time":"2013-06-07T11:08:46Z","timestamp":1370603326000},"page":"1120-1136","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":11,"title":["13C NMR Metabolomic Evaluation of Immediate and Delayed Mild Hypothermia in Cerebrocortical Slices after Oxygen\u2013Glucose Deprivation"],"prefix":"10.1097","volume":"119","author":[{"given":"Jia","family":"Liu","sequence":"first","affiliation":[{"name":"Research Associate"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark R.","family":"Segal","sequence":"additional","affiliation":[{"name":"Professor, The Department of Epidemiology and Biostatistics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark J. S.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Research Associate Professor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey G.","family":"Pelton","sequence":"additional","affiliation":[{"name":"NMR Spectroscopist and Laboratory Manager, QB3 Physical Biosciences Division, Lawrence Berkeley National Laboratory, The University of California, Berkeley, California."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myungwon","family":"Kim","sequence":"additional","affiliation":[{"name":"Visiting Professor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas L.","family":"James","sequence":"additional","affiliation":[{"name":"Professor, The Department of Pharmaceutical Chemistry, The University of California San Francisco, San Francisco, California."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence","family":"Litt","sequence":"additional","affiliation":[{"name":"Professor, The Department 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