{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:03:58Z","timestamp":1790514238146,"version":"4.1.0"},"reference-count":86,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T00:00:00Z","timestamp":1654214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Prophylactic creatine treatment may reduce hypoxic brain injury due to its ability to sustain intracellular ATP levels thereby reducing oxidative and metabolic stress responses during oxygen deprivation. Using microdialysis, we investigated the real\u2010time <jats:italic>in vivo<\/jats:italic> effects of fetal creatine supplementation on cerebral metabolism following acute <jats:italic>in utero<\/jats:italic> hypoxia caused by umbilical cord occlusion (UCO). Fetal sheep (118\u00a0days\u2019 gestational age (dGA)) were implanted with an inflatable Silastic cuff around the umbilical cord and a microdialysis probe inserted into the right cerebral hemisphere for interstitial fluid sampling. Creatine (6\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>\u00a0h<jats:sup>\u22121<\/jats:sup>) or saline was continuously infused intravenously from 122\u00a0dGA. At 131\u00a0dGA, a 10 min UCO was induced. Hourly microdialysis samples were obtained from \u221224 to 72\u00a0h post\u2010UCO and analysed for percentage change of hydroxyl radicals (<jats:sup>\u2022<\/jats:sup>OH) and interstitial metabolites (lactate, pyruvate, glutamate, glycerol, glycine). Histochemical markers of protein and lipid oxidation were assessed at post\u2010mortem 72\u00a0h post\u2010UCO. Prior to UCO, creatine treatment reduced pyruvate and glycerol concentrations in the microdialysate outflow. Creatine treatment reduced interstitial cerebral <jats:sup>\u2022<\/jats:sup>OH outflow 0 to 24\u00a0h post\u2010UCO. Fetuses with higher arterial creatine concentrations before UCO presented with reduced levels of hypoxaemia ( and ) during UCO which associated with reduced interstitial cerebral pyruvate, lactate and <jats:sup>\u2022<\/jats:sup>OH accumulation. No effects of creatine treatment on immunohistochemical markers of oxidative stress were found. In conclusion, fetal creatine treatment decreased cerebral outflow of <jats:sup>\u2022<\/jats:sup>OH and was associated with an improvement in cerebral bioenergetics following acute hypoxia.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15097-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Fetal hypoxia can cause persistent metabolic and oxidative stress responses that disturb energy homeostasis in the brain. Creatine in its phosphorylated form is an endogenous phosphagen; therefore, supplementation is a proposed prophylactic treatment for fetal hypoxia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Fetal sheep instrumented with a cerebral microdialysis probe were continuously infused with or without creatine\u2010monohydrate for 10\u00a0days before induction of 10 min umbilical cord occlusion (UCO; 131\u00a0days\u2019 gestation). Cerebral interstitial fluid was collected up to 72 h following UCO.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Prior to UCO, fetal creatine supplementation reduced interstitial cerebral pyruvate and glycerol concentrations.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Fetal creatine supplementation reduced cerebral hydroxyl radical efflux up to 24 h post\u2010UCO. Fetuses with higher arterial creatine concentrations before UCO and reduced levels of systemic hypoxaemia during UCO were associated with reduced cerebral interstitial pyruvate, lactate and <jats:sup>\u2022<\/jats:sup>OH following UCO.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Creatine supplementation leads to some improvements in cerebral bioenergetics following <jats:italic>in utero<\/jats:italic> acute hypoxia.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp282840","type":"journal-article","created":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T15:00:25Z","timestamp":1652972425000},"page":"3193-3210","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Creatine supplementation reduces the cerebral oxidative and metabolic stress responses to acute <i>in utero<\/i> hypoxia in the late\u2010gestation fetal sheep"],"prefix":"10.1113","volume":"600","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0396-9760","authenticated-orcid":false,"given":"Nhi Thao","family":"Tran","sequence":"first","affiliation":[{"name":"School of Health &amp; 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