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However, this is controversial because there is limited evidence that MgSO\n 4<\/jats:sub>\n provides long\u2010term neuroprotection. Preterm fetal sheep (104\u00a0days gestation; term is 147\u00a0days) were assigned randomly to receive sham occlusion with saline infusion (\n n<\/jats:italic>\n \u00a0=\u00a06) or\n i.v.<\/jats:sc>\n infusion with MgSO\n 4<\/jats:sub>\n (\n n<\/jats:italic>\n \u00a0=\u00a07) or vehicle (saline,\n n<\/jats:italic>\n \u00a0=\u00a06) from 24\u00a0h before hypoxia\u2013ischaemia induced by umbilical cord occlusion until 24\u00a0h after occlusion. Sheep were killed after 21\u00a0days of recovery, for fetal brain histology. Functionally, MgSO\n 4<\/jats:sub>\n did not improve long\u2010term EEG recovery. Histologically, in the premotor cortex and striatum, MgSO\n 4<\/jats:sub>\n infusion attenuated post\u2010occlusion astrocytosis (GFAP\n +<\/jats:sup>\n ) and microgliosis but did not affect numbers of amoeboid microglia or improve neuronal survival. In the periventricular and intragyral white matter, MgSO\n 4<\/jats:sub>\n was associated with fewer total (Olig\u20102\n +<\/jats:sup>\n ) oligodendrocytes compared with vehicle\u00a0+\u00a0occlusion. Numbers of mature (CC1\n +<\/jats:sup>\n ) oligodendrocytes were reduced to a similar extent in both occlusion groups compared with sham occlusion. In contrast, MgSO\n 4<\/jats:sub>\n was associated with an intermediate improvement in myelin density in the intragyral and periventricular white matter tracts. In conclusion, a clinically comparable dose of MgSO\n 4<\/jats:sub>\n was associated with moderate improvements in white and grey matter gliosis and myelin density but did not improve EEG maturation or neuronal or oligodendrocyte survival.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n Magnesium sulphate is widely recommended before preterm birth for neuroprotection; however, there is limited evidence that magnesium sulphate provides long\u2010term neuroprotection.<\/jats:p>\n <\/jats:list-item>\n \n \n In preterm fetal sheep exposed to hypoxia\u2013ischaemia (HI), MgSO\n 4<\/jats:sub>\n was associated with attenuated astrocytosis and microgliosis in the premotor cortex and striatum but did not improve neuronal survival after recovery to term\u2010equivalent age, 21\u00a0days after HI.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Magnesium sulphate was associated with loss of total oligodendrocytes in the periventricular and intragyral white matter tracts, whereas mature, myelinating oligodendrocytes were reduced to a similar extent in both occlusion groups. In the same regions, MgSO\n 4<\/jats:sub>\n was associated with an intermediate improvement in myelin density.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Functionally, MgSO\n 4<\/jats:sub>\n did not improve long\u2010term recovery of EEG power, frequency or sleep stage cycling.\n <\/jats:p>\n <\/jats:list-item>\n \n \n A clinically comparable dose of MgSO\n 4<\/jats:sub>\n was associated with moderate improvements in white and grey matter gliosis and myelin density but did not improve EEG maturation or neuronal or oligodendrocyte survival.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp284381","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T03:55:06Z","timestamp":1680234906000},"page":"1999-2016","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Magnesium sulphate reduces tertiary gliosis but does not improve EEG recovery or white or grey matter cell survival after asphyxia in preterm fetal sheep"],"prefix":"10.1113","volume":"601","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6374-9372","authenticated-orcid":false,"given":"Robert","family":"Galinsky","sequence":"first","affiliation":[{"name":"Department of Physiology University of Auckland Auckland New Zealand"},{"name":"The Ritchie Centre Hudson Institute of Medical Research Clayton Victoria Australia"},{"name":"Department of Obstetrics and Gynaecology Monash University Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simerdeep K.","family":"Dhillon","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharmony B.","family":"Kelly","sequence":"additional","affiliation":[{"name":"The Ritchie Centre Hudson Institute of Medical Research Clayton Victoria Australia"},{"name":"Department of Obstetrics and Gynaecology Monash University Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Wassink","sequence":"additional","affiliation":[{"name":"Department of Physiology 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 University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8937-0846","authenticated-orcid":false,"given":"Christopher A.","family":"Lear","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotte G.","family":"van den Heuij","sequence":"additional","affiliation":[{"name":"Department of Physiology 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 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 University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,13]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(97)70460-5"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1718-6"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-0637-3"},{"issue":"9","key":"e_1_2_5_5_1","first-page":"1837","article-title":"Profound asphyxia in the premature infant: Imaging findings","volume":"16","author":"Barkovich A. 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