缺氧缺血性脑病(HIE)是由于分娩过程中新生儿大脑的血流量和氧气减少引起的。导致婴儿死亡或严重的脑损伤,全球发病率为每1000例活产1.5例。胰高血糖素样肽1受体(GLP1-R)激动剂,用于2型糖尿病的治疗,在各种脑损伤模型中表现出神经保护作用,包括HIE.在这项研究中,我们观察到,在出生后第10天,手术诱导的缺氧缺血性(HI)脑损伤小鼠,在立即全身给药exendin-4或斯马鲁肽后,神经系统结局增强.短期和长期评估显示神经病理学改善,存活率,和运动功能。我们探索了GLP1-R激动剂触发神经保护和减少新生小鼠氧糖剥夺和HI后炎症的机制。强调PI3/AKT信号通路的上调和cAMP水平的升高。这些发现揭示了GLP1-R激动剂在HIE中的神经保护和抗炎作用。可能延伸到其他神经系统疾病,支持他们在治疗HIE婴儿方面的潜在临床应用。
Hypoxic-ischaemic 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-ischaemic (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 signalling 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.