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.

中文翻译：

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糖尿病药物激活新生儿缺氧缺血性脑病模型中的神经保护途径。


缺氧缺血性脑病 (HIE) 是由于分娩期间新生儿大脑血流和氧气减少而引起的，导致婴儿死亡或严重脑损伤，全球发病率为每 1000 名活产儿 1.5 例。用于 2 型糖尿病治疗的胰高血糖素样肽 1 受体 (GLP1-R) 激动剂在包括 HIE 在内的各种脑损伤模型中表现出神经保护作用。在这项研究中，我们观察到，出生后第 10 天手术诱导缺氧缺血 (HI) 脑损伤的小鼠，在立即全身给予 exendin-4 或索马鲁肽后，神经学结果得到改善。短期和长期评估显示神经病理学、存活率和运动功能得到改善。我们探索了 GLP1-R 激动剂触发神经保护并减少新生小鼠氧糖剥夺和 HI 后炎症的机制，强调了 PI3/AKT 信号通路的上调和 cAMP 水平的增加。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，并有可能扩展到其他神经系统疾病，支持其在治疗 HIE 婴儿方面的潜在临床应用。