{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:24:34Z","timestamp":1793060674370,"version":"4.5.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>Insulin-like growth factor-1 (IGF-1) is a single chain polypeptide hormone that plays an essential role in intrauterine and postnatal growth. Recent studies suggest that IGF-1 and its receptor IGF-1R are involved in the pathogenesis of neurological diseases. Here, we explore the effect of IGF-1 signaling in neonatal hypoxic-ischemic (HI) brain injury and elucidate the underlying mechanisms of action. We found that the expression levels of IGF-1 were markedly enhanced in astrocytes post HI. Delivery of IGF-1 significantly alleviates neonatal brain insult and improves neurobehavioral disorders in neonatal mice after HI challenge. Through binding to IGF-1 receptor (IGF-1R), IGF-1 inhibited the apoptosis of neuronal cells following HI exposure. IGF-1 improved neuronal cell survival and proliferation through activation of phosphorylated AKT signaling. Of note, the protective property of IGF-1 against ischemic neuronal insults was dependent on suppression of the FoXO3a-PUMA signaling pathway. Taken together, these findings suggest that IGF-1 may represent a new neuroprotectant for newborns with hypoxic-ischemic encephalopathy.<\/jats:p>","DOI":"10.3389\/fncel.2025.1685800","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T06:24:56Z","timestamp":1762151096000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Neuroprotection of IGF-1 in neonatal hypoxic-ischemic brain injury through downregulation of FoXO3a-PUMA pathway"],"prefix":"10.3389","volume":"19","author":[{"given":"Yanli","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanxia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohong","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengya","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"101191","DOI":"10.1016\/j.molmet.2021.101191","article-title":"Sensory neurons derived from diabetic rats exhibit deficits in functional glycolysis and ATP that are ameliorated by IGF-1.","volume":"49","author":"Aghanoori","year":"2021","journal-title":"Mol. 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