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

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

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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