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It remains unknown whether supplemental IGF-1 may stimulate neurodevelopment in preterm neonates. Using cesarean-delivered preterm pigs as a model of preterm infants, we investigated the effects of supplemental IGF-1 on motor function and on regional and cellular brain development. Pigs were treated with 2.25\u2009mg\/kg\/d recombinant human IGF-1\/IGF binding protein-3 complex from birth until day 5 or 9 before the collection of brain samples for quantitative immunohistochemistry (IHC), RNA sequencing, and quantitative PCR analyses. Brain protein synthesis was measured using<jats:italic>in vivo<\/jats:italic>labeling with [2H5] phenylalanine. We showed that the IGF-1 receptor was widely distributed in the brain and largely coexisted with immature neurons. Region-specific quantification of IHC labeling showed that IGF-1 treatment promoted neuronal differentiation, increased subcortical myelination, and attenuated synaptogenesis in a region-dependent and time-dependent manner. The expression levels of genes involved in neuronal and oligodendrocyte maturation, and angiogenic and transport functions were altered, reflecting enhanced brain maturation in response to IGF-1 treatment. Cerebellar protein synthesis was increased by 19% at day 5 and 14% at day 9 after IGF-1 treatment. Treatment had no effect on Iba1<jats:sup>+<\/jats:sup>microglia or regional brain weights and did not affect motor development or the expression of genes related to IGF-1 signaling. In conclusion, the data show that supplemental IGF-1 promotes brain maturation in newborn preterm pigs. The results provide further support for IGF-1 supplementation therapy in the early postnatal period in preterm infants.<\/jats:p>","DOI":"10.1523\/eneuro.0430-22.2023","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T17:50:14Z","timestamp":1679939414000},"page":"ENEURO.0430-22.2023","source":"Crossref","is-referenced-by-count":16,"title":["Insulin-Like Growth Factor-1 Supplementation Promotes Brain Maturation in Preterm Pigs"],"prefix":"10.1523","volume":"10","author":[{"given":"Line I.","family":"Christiansen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Holmqvist","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristine","family":"Holgersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandy E. 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