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More information is needed about the mechanisms mediating the effect of MgSO<jats:sub>4<\/jats:sub> on seizures and sexual dimorphism, and the influence of circadian rhythms on seizure expression.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Seizures are common in newborns after asphyxia at birth and are often refractory to anti\u2010seizure agents. Magnesium sulphate (MgSO<jats:sub>4<\/jats:sub>) has anticonvulsant effects and is increasingly given to women in preterm labour for potential neuroprotection. There is limited information on its effects on perinatal seizures. We examined the hypothesis that MgSO<jats:sub>4<\/jats:sub> infusion would reduce fetal seizures after asphyxia <jats:italic>in utero<\/jats:italic>. Preterm fetal sheep at 0.7 gestation (104\u00a0days, term\u00a0=\u00a0147\u00a0days) were given intravenous infusions of either saline (<jats:italic>n<\/jats:italic>\u00a0=\u00a014) or MgSO<jats:sub>4<\/jats:sub> (<jats:italic>n<\/jats:italic>\u00a0=\u00a012, 160\u00a0mg bolus\u00a0+\u00a048\u00a0mg\u00a0h<jats:sup>\u22121<\/jats:sup> infusion over 48\u00a0h). Fetuses underwent umbilical cord occlusion (UCO) for 25\u00a0min, 24\u00a0h after the start of infusion. The start time for seizures did not differ between groups, but MgSO<jats:sub>4<\/jats:sub> significantly reduced the total number of seizures (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), peak seizure amplitude (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and seizure burden (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.005). Within the saline\u2010asphyxia group, male fetuses had significantly more seizures than females (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Within the MgSO<jats:sub>4<\/jats:sub>\u2010asphyxia group, although both sexes had fewer seizures than the saline\u2010asphyxia group, the greatest effect of MgSO<jats:sub>4<\/jats:sub> was on male fetuses, with reduced numbers of seizures (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) and seizure burden (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.005). Only 1 out of 6 MgSO<jats:sub>4<\/jats:sub> males had seizures on the second day post\u2010UCO compared to 5 out of 6 MgSO<jats:sub>4<\/jats:sub> female fetuses (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.08). Finally, seizures showed a circadian profile with peak seizures between 04.00 and 06.00\u00a0h on the first and second day post\u2010UCO. Collectively, these results suggest that MgSO<jats:sub>4<\/jats:sub> may have utility in treating perinatal seizures and has sexually dimorphic effects.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp275627","type":"journal-article","created":{"date-parts":[[2018,3,24]],"date-time":"2018-03-24T01:34:04Z","timestamp":1521855244000},"page":"6079-6092","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Time and sex dependent effects of magnesium sulphate on post\u2010asphyxial seizures in preterm fetal sheep"],"prefix":"10.1113","volume":"596","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4336-7596","authenticated-orcid":false,"given":"Laura","family":"Bennet","sequence":"first","affiliation":[{"name":"The Fetal Physiology and Neuroscience Group, The Department of Physiology The University of Auckland  Auckland New 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