Department of Neurology, The Second Affiliated Hospital of Shanxi Medical University, No. 382 Wuyi Road, Taiyuan, 030001, Shanxi Province, China.
Department of Neurology, The Second Affiliated Hospital of Shanxi Medical University, No. 382 Wuyi Road, Taiyuan, 030001, Shanxi Province, China.
Neuropharmacology. 2019 Nov 1;158:107748. doi: 10.1016/j.neuropharm.2019.107748. Epub 2019 Aug 26.
Stroke is a condition with few medical treatments available. Semaglutide, a novel Glucagon-like peptide-1 (GLP-1) analogue, has been brought to the market as a treatment for diabetes. We tested the protective effects of semaglutide against middle cerebral artery occlusion injury in rats. Animals were treated with 10 nmol/kg bw ip. starting 2 h after surgery and every second day for either 1, 7, 14 or 21 days. Semaglutide-treated animals showed significantly reduced scores of neurological impairments in several motor and grip strength tasks. The cerebral infarction size was also reduced, and the loss of neurons in the hippocampal areas CA1, CA3 and the dentate gyrus was much reduced. Chronic inflammation as seen in levels of activated microglia and in the activity of the p38 MAPK - MKK - c-Jun- NF-κB p65 inflammation signaling pathway was reduced. In addition, improved growth factor signaling as shown in levels of activated ERK1 and IRS-1, and a reduction in the apoptosis signaling pathway C-raf, ERK2, Bcl-2/BAX and Caspase-3 was observed. Neurogenesis had also been normalized by the drug treatment as seen in increased neurogenesis (DCX-positive cells) in the dentate gyrus and a normalization of biomarkers for neurogenesis. In conclusion, semaglutide is a promising candidate for re-purposing as a stroke treatment.
中风是一种治疗方法有限的疾病。作为治疗糖尿病的新的胰高血糖素样肽-1（GLP-1）类似物，司美格鲁肽已被推向市场。我们测试了司美格鲁肽对大鼠大脑中动脉闭塞损伤的保护作用。动物在手术后 2 小时开始接受 10nmol/kg bw ip 治疗，每两天一次，持续 1、7、14 或 21 天。与对照组相比，司美格鲁肽治疗组在多项运动和握力任务中的神经损伤评分显著降低。脑梗死面积也减小，海马区 CA1、CA3 和齿状回神经元丢失明显减少。慢性炎症表现为激活的小胶质细胞水平和 p38 MAPK-MKK-c-Jun-NF-κB p65 炎症信号通路的活性降低。此外，还观察到生长因子信号的改善，表现为激活的 ERK1 和 IRS-1 水平升高，以及凋亡信号通路 C-raf、ERK2、Bcl-2/BAX 和 Caspase-3 的减少。药物治疗还使神经发生正常化，表现为齿状回中神经发生（DCX 阳性细胞）增加和神经发生的生物标志物正常化。总之，司美格鲁肽是一种很有前途的再利用为中风治疗的候选药物。
