IGF-1 ameliorates the blood brain barrier disruption induced by the neonatal hypoxia-ischemia

  • Int Immunopharmacol. 2026 Mar 15:173:116323. doi: 10.1016/j.intimp.2026.116323.
Rui Zhong  1 ,  Haiqing Huang  2 ,  Jiayi Liang  3 ,  Wei Lai  1 ,  Yingyin Tan  2 ,  Wanxia Liu  2 ,  Baohong Yuan  1 ,  Zhenhui He  4 ,  Yanli Tang  5 ,  Tao Liu  6 ,  Hui Yin  7
Affiliations
  • 1. Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou 510006, China.
  • 2. Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China.
  • 3. Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China.
  • 4. Department of Clinical Laboratory Technology, Medical School, Foshan University, Foshan 528000, China.
  • 5. Longgang District Maternity & Child Healthcare Hospital of Shenzhen City, (Affiliated Shenzhen Women and Children's Hospital (Longgang) of Shantou University Medical College), Shenzhen 518172, China.
  • 6. Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: [email protected].
  • 7. Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: [email protected].
PMID: 41655435 DOI: 10.1016/j.intimp.2026.116323
Abstract

Neonatal hypoxic-ischemic encephalopathy (HIE) disrupts the blood-brain barrier (BBB) and destroys nascent vessels, thereby amplifying parenchymal loss and chronic neurological disability. Restoring a competent cerebrovasculature is therefore a critical therapeutic goal. Insulin-like growth factor-1 (IGF-1) is already recognized as a neurotrophic factor whose circulating levels correlate with HIE severity and long-term outcome, yet its capacity to drive vascular repair after the insult remains incompletely defined. This study investigated the role of exogenous IGF-1 in BBB repair in neonatal mouse post HI. Our results showed that IGF-1 receptor (IGF-1R) existed on the surface of endothelial cells, which was further upregulated in response to HI challenge. Administration of exogenous IGF-1 apparently attenuated BBB disruption concomitant with a marked enhancement of angiogenesis within the injured cerebral parenchyma. On the contrary, inhibition of the IGF-1R abrogated IGF-1-mediated proangiogenic effects. More importantly, activation of the IGF-1/IGF-1R axis promotes revascularization dependent on upregulation of Akt/eNOS signaling. All together, these findings indicate that IGF-1/IGF-1R axis may represent a potential therapeutic target for blood-brain barrier repair in neonatal HI injury.

Keywords
Angiogenesis; Blood-brain barrier (BBB); Hypoxic-ischemic encephalopathy (HIE); IGF-1; eNOS.
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