ORIGINAL RESEARCH article
Front. Cell. Neurosci.
Sec. Cellular Neuropathology
Volume 19 - 2025 | doi: 10.3389/fncel.2025.1685800
Neuroprotection of IGF-1 in neonatal hypoxic-ischemic brain injury through downregulation of FoXO3a-PUMA pathway
Provisionally accepted
- 1Longgang District Maternity & Child Healthcare Hospital of Shenzhen City, Shenzhen, China
- 2Guangdong Pharmaceutical University, Guangzhou, China
- 3Jiangxi Provincial People's Hospital, Nanchang, China
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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.
Keywords: IGF-1, Neonatal hypoxic-ischemic encephalopathy, Neuroprotection, FoxO3a, Puma
Received: 14 Aug 2025; Accepted: 21 Oct 2025.
Copyright: © 2025 Tang, Zhong, Liang, Liu, Liu, LIU, Yuan, Jiao and Yin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hui Yin, huiyin0103@163.com
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