{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:03:43Z","timestamp":1789495423060,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:00:00Z","timestamp":1731369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>The optimal rate of rewarming after therapeutic hypothermia is unclear. Slow rewarming may reduce cardiovascular instability and rebound seizures, but there is little controlled evidence to support this. The present study aimed to determine whether slow rewarming can improve neuroprotection after 72\u00a0h of hypothermia. Fetal sheep (0.85 gestation) received sham occlusion (<jats:italic>n<\/jats:italic>\u00a0=\u00a08) or 30\u00a0min of global cerebral ischaemia followed by normothermia (<jats:italic>n<\/jats:italic>\u00a0=\u00a07), or hypothermia from 3 to 72\u00a0h with either fast, spontaneous rewarming within 1\u00a0h (<jats:italic>n<\/jats:italic>\u00a0=\u00a08) or slow rewarming at 0.5\u00b0C\u00a0h<jats:sup>\u22121<\/jats:sup> over 10\u00a0h (<jats:italic>n<\/jats:italic>\u00a0=\u00a08). Hypothermia improved EEG and spectral edge recovery, with no significant difference between fast and slow rewarming. Hypothermia reduced the number of seizures, with no significant difference in seizure activity between fast and slow rewarming. Hypothermia improved neuronal survival in the cortex, CA1, CA3, CA4 and dentate gyrus regions of the hippocampus, with no significant difference between fast and slow rewarming. Hypothermia attenuated microglia counts in the cortex, with no significant difference between fast and slow rewarming. The rate of rewarming after a clinically relevant duration of hypothermia did not affect neurophysiological recovery, neuronal survival or attenuation of microglia after global cerebral ischaemia in term\u2010equivalent fetal sheep.\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\/tjp16406-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>The rate of rewarming after 72\u00a0h of hypothermia did not affect recovery of EEG or spectral edge.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>There was no difference in the occurrence of seizures as a result of the rate of rewarming after hypothermia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The rate of rewarming after 72\u00a0h of hypothermia did not affect neuronal survival in the cortex or hippocampus.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp287453","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T12:34:20Z","timestamp":1731414860000},"page":"7085-7101","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Lack of additional benefit from slow rewarming after therapeutic hypothermia for ischaemic brain injury in near\u2010term fetal sheep"],"prefix":"10.1113","volume":"602","author":[{"given":"Alice","family":"McDouall","sequence":"first","affiliation":[{"name":"Department of Physiology the University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly Q.","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Physiology the University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Wassink","sequence":"additional","affiliation":[{"name":"Department of Physiology the University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Davies","sequence":"additional","affiliation":[{"name":"Department of Physiology the University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4336-7596","authenticated-orcid":false,"given":"Laura","family":"Bennet","sequence":"additional","affiliation":[{"name":"Department of Physiology the University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0656-7035","authenticated-orcid":false,"given":"Alistair J.","family":"Gunn","sequence":"additional","affiliation":[{"name":"Department of Physiology the University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6781-4258","authenticated-orcid":false,"given":"Joanne O.","family":"Davidson","sequence":"additional","affiliation":[{"name":"Department of Physiology the University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,12]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1315788"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0900854"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2004-1695"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clp.2024.04.002"},{"issue":"12","key":"e_1_2_5_6_1","first-page":"1484","article-title":"Association between increased seizures during rewarming after hypothermia for neonatal hypoxic ischemic encephalopathy and abnormal neurodevelopmental outcomes at 2\u2010year follow\u2010up: A nested multisite cohort study","volume":"78","author":"Chalak L. 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