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Insulin-like growth factor-1 can reduce acute brain injury, but its effects on chronic white matter injury after hypoxia-ischaemia are unclear. Preterm-equivalent foetal sheep (0.6 gestation) received either sham-asphyxia or asphyxia induced by umbilical cord occlusion for 30\u2005min, and recovered for either 3 or 35 days after asphyxia. The 35 day recovery groups received either an intracerebroventricular infusion of insulin-like growth factor-1 (1\u2005\u00b5g\/24\u2005h) or vehicle, from 3 to 14 days after asphyxia. Asphyxia was associated with ventricular enlargement, and loss of frontal and parietal white matter area (P &amp;lt; 0.05 versus sham-asphyxia). This was associated with reduced area fraction of myelin basic protein and numbers of oligodendrocyte transcription factor 2 and mature, anti-adenomatous polyposis coli-positive oligodendrocytes in periventricular white matter (P &amp;lt; 0.05), with persistent inflammation and caspase-3 activation (P &amp;lt; 0.05). Four of eight foetuses developed cystic lesions in temporal white matter. Prolonged infusion with insulin-like growth factor-1 restored frontal white matter area, improved numbers of oligodendrocyte transcription factor 2-positive and mature, anti-adenomatous polyposis coli-positive oligodendrocytes, with reduced astrogliosis and microgliosis after 35 days recovery (P &amp;lt; 0.05 versus asphyxia). One of four foetuses developed temporal cystic lesions. Functionally, insulin-like growth factor-1-treated foetuses had faster recovery of EEG power, but not spectral edge. Encouragingly, these findings show that delayed, prolonged, insulin-like growth factor-1 treatment can improve functional maturation of periventricular white matter after severe asphyxia in the very immature brain, at least in part by suppressing chronic neural inflammation.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae373","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T18:32:33Z","timestamp":1729794753000},"source":"Crossref","is-referenced-by-count":2,"title":["White matter protection with insulin-like growth factor-1 after hypoxia-ischaemia in preterm foetal sheep"],"prefix":"10.1093","volume":"6","author":[{"given":"Guido","family":"Wassink","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Auckland , Private Bag 92019, Auckland 1023 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenta H T","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Auckland , Private Bag 92019, Auckland 1023 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Mathai","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Auckland , Private Bag 92019, Auckland 1023 ,","place":["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 , Private Bag 92019, Auckland 1023 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1377-0878","authenticated-orcid":false,"given":"Justin M","family":"Dean","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Auckland , Private Bag 92019, Auckland 1023 ,","place":["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 , Private Bag 92019, Auckland 1023 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Bennet","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Auckland , Private Bag 92019, Auckland 1023 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,10,24]]},"reference":[{"key":"2024122016245379500_fcae373-B1","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1136\/archdischild-2020-320650","article-title":"No change in neurodevelopment at 11 years after extremely preterm 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