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Diabetes drugs activate neuroprotective pathways in neonatal hypoxic-ischemic encephalopathy models

ABSTRACT: Hypoxic-ischemic encephalopathy (HIE) arises from diminished blood flow and oxygen to the neonatal brain during labor, leading to infant mortality or severe brain damage, with a global incidence of 1.5 per 1000 live births. Glucagon-like Peptide 1 Receptor (GLP1-R) agonists, used in type 2 diabetes treatment, exhibit neuroprotective effects in various brain injury models, including HIE. In this study, we observed enhanced neurological outcomes in post-natal day 10 mice with surgically induced hypoxic-ischemic (HI) brain injury after immediate systemic administration of exendin-4 or semaglutide. Short- and long-term assessments revealed improved neuropathology, survival rates, and locomotor function. We explored the mechanisms by which GLP1-R agonists trigger neuroprotection and reduce inflammation following oxygen-glucose deprivation and HI in neonatal mice, highlighting the upregulation of the PI3/AKT signaling pathway and increased cAMP levels. These findings shed light on the neuroprotective and anti-inflammatory effects of GLP1-R agonists in HIE, potentially extending to other neurological conditions, supporting their potential clinical use in treating infants with HIE.

SUBMITTER: Dr. Laura Poupon-Bejuit

PROVIDER: S-SCDT-10_1038-S44321-024-00079-1 | biostudies-other |

REPOSITORIES: biostudies-other

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Neuroprotective Strategies after Neonatal Hypoxic Ischemic Encephalopathy.

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