{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T12:14:56Z","timestamp":1785500096890,"version":"3.56.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2019,7,29]],"date-time":"2019-07-29T00:00:00Z","timestamp":1564358400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2019,7,29]],"date-time":"2019-07-29T00:00:00Z","timestamp":1564358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Res"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1038\/s41390-019-0511-8","type":"journal-article","created":{"date-parts":[[2019,7,29]],"date-time":"2019-07-29T10:21:36Z","timestamp":1564395696000},"page":"699-708","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Short-term effects of early initiation of magnesium infusion combined with cooling after hypoxia\u2013ischemia in term piglets"],"prefix":"10.1038","volume":"86","author":[{"given":"Ingran","family":"Lingam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Meehan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adnan","family":"Avdic-Belltheus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Martinello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariya","family":"Hristova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pardis","family":"Kaynezhad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelius","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilias","family":"Tachtsidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Golay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola J.","family":"Robertson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,7,29]]},"reference":[{"key":"511_CR1","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1001\/jamapediatrics.2015.4276","volume":"170","author":"Global Burden of Disease Pediatrics Collaboration","year":"2016","unstructured":"Global Burden of Disease Pediatrics Collaboration et al.Global and national burden of diseases and injuries among children and adolescents between 1990 and 2013: findings from the Global Burden of Disease 2013 Study. JAMA Pediatr. 170, 267\u2013287 (2016).","journal-title":"JAMA Pediatr."},{"key":"511_CR2","doi-asserted-by":"crossref","unstructured":"Jacobs, S. E. et al. Cooling for newborns with hypoxic ischaemic encephalopathy (Review). Cochrane Database Syst. Rev. CD003311 (2013).","DOI":"10.1002\/14651858.CD003311.pub3"},{"key":"511_CR3","doi-asserted-by":"publisher","first-page":"2629","DOI":"10.1001\/jama.2014.16058","volume":"312","author":"S Shankaran","year":"2014","unstructured":"Shankaran, S. et al. Effect of depth and duration of cooling on deaths in the NICU among neonates with hypoxic ischemic encephalopathy: a randomized clinical trial. JAMA 312, 2629\u20132639 (2014).","journal-title":"JAMA"},{"key":"511_CR4","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1001\/jama.2014.11189","volume":"312","author":"LW Doyle","year":"2014","unstructured":"Doyle, L. W., Anderson, P. J., Haslam, R., Lee, K. J. & Crowther, C. School-age outcomes of very preterm infants after antenatal treatment with magnesium sulfate vs placebo. JAMA 312, 1105\u20131113 (2014).","journal-title":"JAMA"},{"key":"511_CR5","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1385\/NCC:2:3:342","volume":"2","author":"JA McKee","year":"2005","unstructured":"McKee, J. A. et al. Magnesium neuroprotection is limited in humans with acute brain injury. Neurocrit. Care 2, 342\u2013351 (2005).","journal-title":"Neurocrit. Care"},{"key":"511_CR6","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1007\/s00701-005-0496-4","volume":"147","author":"T Westermaier","year":"2005","unstructured":"Westermaier, T., Zausinger, S., Baethmann, A. & Schmid-Elsaesser, R. Dose finding study of intravenous magnesium sulphate in transient focal cerebral ischemia in rats. Acta Neurochir. 147, 525\u2013532 (2005).","journal-title":"Acta Neurochir."},{"key":"511_CR7","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1159\/000362206","volume":"36","author":"R Galinsky","year":"2014","unstructured":"Galinsky, R. et al. Magnesium is not consistently neuroprotective for perinatal hypoxia-ischemia in term-equivalent models in preclinical studies: a systematic review. Dev. Neurosci. 36, 73\u201382 (2014).","journal-title":"Dev. Neurosci."},{"key":"511_CR8","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1203\/00006450-199703000-00024","volume":"41","author":"J Penrice","year":"1997","unstructured":"Penrice, J. et al. Magnesium sulfate after transient hypoxia-ischemia fails to prevent delayed cerebral energy failure in the newborn piglet. Pediatr. Res. 41, 443\u2013447 (1997).","journal-title":"Pediatr. Res."},{"key":"511_CR9","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1038\/jp.2013.65","volume":"33","author":"M Tagin","year":"2013","unstructured":"Tagin, M., Shah, P. S. & Lee, K.-S. Magnesium for newborns with hypoxic-ischemic encephalopathy: a systematic review and meta-analysis. J. Perinatol. 33, 663\u2013669 (2013).","journal-title":"J. Perinatol."},{"issue":"6","key":"511_CR10","doi-asserted-by":"publisher","first-page":"851.e1-851.e8","DOI":"10.1016\/j.ajog.2015.07.042","volume":"213","author":"Vered B. Lamhot","year":"2015","unstructured":"Lamhot, V. B. et al. Magnesium sulfate prevents maternal inflammation-induced impairment of learning ability and memory in rat offspring. Am. J. Obstet. Gynecol. 213, 851.e1\u2013851.e8 (2015).","journal-title":"American Journal of Obstetrics and Gynecology"},{"key":"511_CR11","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1038\/jcbfm.2012.83","volume":"32","author":"DD Jenkins","year":"2012","unstructured":"Jenkins, D. D. et al. Serum cytokines in a clinical trial of hypothermia for neonatal hypoxic-ischemic encephalopathy. J. Cereb. Blood Flow Metab. 32, 1888\u20131896 (2012).","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"511_CR12","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.expneurol.2005.01.022","volume":"193","author":"H Zhu","year":"2005","unstructured":"Zhu, H., Meloni, B. P., Bojarski, C., Knuckey, M. W. & Knuckey, N. W. Post-ischemic modest hypothermia (35C) combined with intravenous magnesium is more effective at reducing CA1 neuronal death than either treatment used alone following global cerebral ischemia in rats. Exp. Neurol. 193, 361\u2013368 (2005).","journal-title":"Exp. Neurol."},{"key":"511_CR13","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1093\/brain\/aws285","volume":"136","author":"NJ Robertson","year":"2013","unstructured":"Robertson, N. J. et al. Melatonin augments hypothermic neuroprotection in a perinatal asphyxia model. Brain 136, 90\u2013105 (2013).","journal-title":"Brain"},{"key":"511_CR14","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1006\/jmre.1997.1244","volume":"129","author":"L Vanhamme","year":"1997","unstructured":"Vanhamme, L., van den Boogaart, A. & Van Huffel, S. Improved method for accurate and efficient quantification of MRS data with use of prior knowledge. J. Magn. Reson. 129, 35\u201343 (1997).","journal-title":"J. Magn. Reson."},{"key":"511_CR15","doi-asserted-by":"publisher","first-page":"e76","DOI":"10.1542\/neo.7-2-e76","volume":"7","author":"L Hellstrom-Westas","year":"2006","unstructured":"Hellstrom-Westas, L., Rosen, I., de Vries, L. S. & Greisen, G. Amplitude-integrated EEG classification and interpretation in preterm and term infants. Neoreviews 7, e76\u201387 (2006).","journal-title":"Neoreviews"},{"key":"511_CR16","doi-asserted-by":"publisher","first-page":"091307","DOI":"10.1117\/1.JBO.21.9.091307","volume":"21","author":"G Bale","year":"2016","unstructured":"Bale, G., Elwell, C. E. & Tachtsidis, I. From J\u00f6bsis to the present day: a review of clinical near-infrared spectroscopy measurements of cerebral cytochrome-c-oxidase. J. Biomed. Opt. 21, 091307 (2016).","journal-title":"J. Biomed. Opt."},{"key":"511_CR17","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.neuroimage.2013.08.016","volume":"102","author":"A Bainbridge","year":"2014","unstructured":"Bainbridge, A. et al. Brain mitochondrial oxidative metabolism during and after cerebral hypoxia-ischemia studied by simultaneous phosphorus magnetic-resonance and broadband near-infrared spectroscopy. Neuroimage 102, 173\u2013183 (2014).","journal-title":"Neuroimage"},{"issue":"2","key":"511_CR18","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1002\/(SICI)1098-1136(199606)17:2<121::AID-GLIA4>3.0.CO;2-5","volume":"17","author":"J. Carsten M\u00f6ller","year":"1996","unstructured":"M\u00f6ller, J. C. et al. Regulation of thrombospondin in the regenerating mouse facial motor nucleus. Glia 17, 121\u2013132 (1996).","journal-title":"Glia"},{"issue":"3","key":"511_CR19","doi-asserted-by":"publisher","first-page":"158","DOI":"10.4103\/2249-4847.159863","volume":"4","author":"SajjadUr Rahman","year":"2015","unstructured":"Rahman, S. et al. Multicenter randomized controlled trial of therapeutic hypothermia plus magnesium sulfate versus therapeutic hypothermia plus placebo in the management of term and near-term infants with hypoxic ischemic encephalopathy (The Mag Cool study): a pilot study. J. Clin. Neonatol. 4, 158\u2013163 (2015).","journal-title":"Journal of Clinical Neonatology"},{"key":"511_CR20","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1684\/mrh.2009.0167","volume":"22","author":"GKC Wong","year":"2009","unstructured":"Wong, G. K. C., Lam, C. W. K., Chan, M. T. V., Gin, T. & Poon, W. S. The effect of hypermagnesemic treatment on cerebrospinal fluid magnesium level in patients with aneurysmal subarachnoid hemorrhage. Magnes. Res. 22, 60\u201365 (2009).","journal-title":"Magnes. Res."},{"key":"511_CR21","first-page":"303","volume":"5","author":"ME Morris","year":"1992","unstructured":"Morris, M. E. Brain and CSF magnesium concentrations during magnesium deficit in animals and humans: neurological symptoms. Magnes. Res. 5, 303\u2013313 (1992).","journal-title":"Magnes. Res."},{"key":"511_CR22","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1089\/ther.2011.0007","volume":"1","author":"L-X Li","year":"2011","unstructured":"Li, L.-X., Campbell, K., Zhao, S., Knuckey, N. W. & Meloni, B. P. Comparison of the efficacy of mild hypothermia (35\u2009\u00b0C) and moderate hypothermia (33\u2009\u00b0C), alone or combined with magnesium treatment, when commenced 2 or 4\u2009h after global cerebral ischemia in rats. Ther. Hypothermia Temp. Manag. 1, 151\u2013158 (2011).","journal-title":"Ther. Hypothermia Temp. Manag."},{"key":"511_CR23","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1097\/01.WCB.0000053472.41007.F9","volume":"23","author":"D Dewar","year":"2003","unstructured":"Dewar, D., Underhill, S. M. & Goldberg, M. P. Oligodendrocytes and ischemic brain injury. J. Cereb. Blood Flow. Metab. 23, 263\u2013274 (2003).","journal-title":"J. Cereb. Blood Flow. Metab."},{"issue":"4","key":"511_CR24","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1177\/0271678X16655548","volume":"37","author":"Robert Galinsky","year":"2016","unstructured":"Galinsky, R. et al. Magnesium sulfate reduces EEG activity but is not neuroprotective after asphyxia in preterm fetal sheep. J. Cereb. Blood Flow Metab. 37, 1362\u20131373 (2017).","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"key":"511_CR25","doi-asserted-by":"crossref","unstructured":"Charriaut-Marlangue, C., Besson, V. C. & Baud, O. Sexually dimorphic outcomes after neonatal stroke and hypoxia-ischemia. Int. J. Mol. Sci. 19, E61 (2018).","DOI":"10.3390\/ijms19010061"},{"key":"511_CR26","doi-asserted-by":"crossref","unstructured":"Cho, B. B. & Toledo-Pereyra, L. H. Caspase-independent programmed cell death following ischemic stroke. J. Investig. Surg. 21, 141\u2013147 (2008).","DOI":"10.1080\/08941930802029945"},{"key":"511_CR27","doi-asserted-by":"crossref","unstructured":"Abraham, M. C. & Shaham, S. Death without caspases, caspases without death. Trends Cell Biol. 14, 184\u2013193 (2004).","DOI":"10.1016\/j.tcb.2004.03.002"},{"key":"511_CR28","doi-asserted-by":"publisher","first-page":"e15328","DOI":"10.1371\/journal.pone.0015328","volume":"5","author":"S McComb","year":"2010","unstructured":"McComb, S., Mulligan, R. & Sad, S. Caspase-3 is transiently activated without cell death during early antigen driven expansion of CD8+ T cells in vivo. PLoS ONE 5, e15328 (2010).","journal-title":"PLoS ONE"},{"key":"511_CR29","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1002\/ana.22419","volume":"69","author":"FJ Northington","year":"2011","unstructured":"Northington, F. J., Chavez-Valdez, R. & Martin, L. J. Neuronal cell death in neonatal hypoxia-ischemia. Ann. Neurol. 69, 743\u2013758 (2011).","journal-title":"Ann. Neurol."},{"key":"511_CR30","unstructured":"Pang, R. et al. 1H MRS Lactate\/N-acetylaspartate is associated with whole brain cell death and inflammation in a piglet model of perinatal asphyxia. Paediatr. Acad. Soc. Abstr. E-PAS2019:4153.49 (2019)."},{"key":"511_CR31","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/dmcn.12726","volume":"57","author":"N Merchant","year":"2015","unstructured":"Merchant, N. & Azzopardi, D. Early predictors of outcome in infants treated with hypothermia for hypoxic-ischaemic encephalopathy. Dev. Med. Child Neurol. 57, 8\u201316 (2015).","journal-title":"Dev. Med. Child Neurol."},{"key":"511_CR32","doi-asserted-by":"publisher","first-page":"e131","DOI":"10.1542\/peds.2009-2938","volume":"126","author":"M Thoresen","year":"2010","unstructured":"Thoresen, M., Hellstr\u00f6m-Westas, L., Liu, X. & de Vries, L. S. Effect of hypothermia on amplitude-integrated electroencephalogram in infants with asphyxia. Pediatrics 126, e131\u2013e139 (2010).","journal-title":"Pediatrics"},{"key":"511_CR33","doi-asserted-by":"publisher","first-page":"6079","DOI":"10.1113\/JP275627","volume":"596","author":"L Bennet","year":"2018","unstructured":"Bennet, L. et al. Time and sex dependent effects of magnesium sulphate on post-asphyxial seizures in preterm fetal sheep. J. Physiol. 596, 6079\u20136092 (2018).","journal-title":"J. Physiol."},{"key":"511_CR34","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1002\/ana.24967","volume":"82","author":"D Torolira","year":"2017","unstructured":"Torolira, D., Suchomelova, L., Wasterlain, C. G. & Niquet, J. Phenobarbital and midazolam increase neonatal seizure-associated neuronal injury. Ann. Neurol. 82, 115\u2013120 (2017).","journal-title":"Ann. Neurol."},{"key":"511_CR35","doi-asserted-by":"publisher","first-page":"e382","DOI":"10.1542\/peds.2009-1046","volume":"125","author":"S Thayyil","year":"2010","unstructured":"Thayyil, S. et al. Cerebral magnetic resonance biomarkers in neonatal encephalopathy: a meta-analysis. Pediatrics 125, e382\u2013e395 (2010).","journal-title":"Pediatrics"},{"key":"511_CR36","doi-asserted-by":"publisher","first-page":"37","DOI":"10.2174\/157339631001140408120613","volume":"10","author":"NJ Robertson","year":"2014","unstructured":"Robertson, N. J., Thayyil, S., Cady, E. B. & Raivich, G. Magnetic resonance spectroscopy biomarkers in term perinatal asphyxial encephalopathy: from neuropathological correlates to future clinical applications. Curr. Pediatr. Rev. 10, 37\u201347 (2014).","journal-title":"Curr. Pediatr. Rev."},{"key":"511_CR37","doi-asserted-by":"publisher","first-page":"6338","DOI":"10.4049\/jimmunol.1101765","volume":"188","author":"J Sugimoto","year":"2012","unstructured":"Sugimoto, J. et al. Magnesium decreases inflammatory cytokine production: a novel innate immunomodulatory mechanism. J. Immunol. 188, 6338\u20136346 (2012).","journal-title":"J. Immunol."},{"key":"511_CR38","doi-asserted-by":"publisher","first-page":"364.e1","DOI":"10.1016\/j.ajog.2010.11.006","volume":"204","author":"HB Tam Tam","year":"2011","unstructured":"Tam Tam, H. B. et al. Magnesium sulfate ameliorates maternal and fetal inflammation in a rat model of maternal infection. Am. J. Obstet. Gynecol. 204, 364.e1\u20138 (2011).","journal-title":"Am. J. Obstet. Gynecol."},{"key":"511_CR39","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1002\/ana.22387","volume":"70","author":"S Faulkner","year":"2011","unstructured":"Faulkner, S. et al. Xenon augmented hypothermia reduces early lactate\/N-acetylaspartate and cell death in perinatal asphyxia. Ann. Neurol. 70, 133\u2013150 (2011).","journal-title":"Ann. Neurol."},{"key":"511_CR40","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1203\/00006450-199505000-00019","volume":"37","author":"M Thoresen","year":"1995","unstructured":"Thoresen, M. et al. Mild hypothermia after severe transient hypoxia-ischemia ameliorates delayed cerebral energy failure in the newborn piglet. Pediatr. Res. 37, 667 (1995).","journal-title":"Pediatr. Res."}],"container-title":["Pediatric Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41390-019-0511-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-019-0511-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-019-0511-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T06:01:59Z","timestamp":1744178519000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41390-019-0511-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,29]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["511"],"URL":"https:\/\/doi.org\/10.1038\/s41390-019-0511-8","relation":{},"ISSN":["0031-3998","1530-0447"],"issn-type":[{"value":"0031-3998","type":"print"},{"value":"1530-0447","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,29]]},"assertion":[{"value":"4 April 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 July 2019","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2019","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 July 2019","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}