Wang Rui-Fang, Xue Guo-Fang, Hölscher Christian, Tian Miao-Jing, Feng Peng, Zheng Ji-Ying, Li Dong-Fang
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.
Epilepsy Res. 2018 May;142:45-52. doi: 10.1016/j.eplepsyres.2018.03.009. Epub 2018 Mar 9.
Glucagon-like peptide-1(GLP-1) is a growth factor that has neuroprotective and anti-inflammatory properties. The protease resistant GLP-1 analogue liraglutide has been shown to be neuroprotective in previous studies in animal models of Alzheimer's disease or Parkinson's disease. Status epilepticus (SE) is a complex disorder, involving many underlying pathological processes, including excitotoxic and chronic inflammatory events. The present pilot study aims to investigate whether liraglutide alleviates the chronic inflammation response and mitochondrial stress induced by SE in the lithium-pilocarpine animal model. We found that treatment with 25nmol/kg. i.p. once-daily after the induction of SE for 7 days reduced chronic inflammation as shown by reduced numbers of activated microglia and astrocytes, and reduced levels of TNF-α and IL-1ß in the hippocampus. The mitochondrial stress marker BAX was reduced and the survival factor Bcl-2 was enhanced by liraglutide. Blood glucose levels were not affected by liraglutide. We show for the first time that liraglutide can reduce the chronic inflammation and mitochondrial stress induced by SE, and the results suggest that GLP-1 receptor agonists such as liraglutide have restorative and protective effects in the brain after SE and could serve as a potential treatment.
胰高血糖素样肽-1（GLP-1）是一种具有神经保护和抗炎特性的生长因子。在先前针对阿尔茨海默病或帕金森病动物模型的研究中，蛋白酶抗性GLP-1类似物利拉鲁肽已被证明具有神经保护作用。癫痫持续状态（SE）是一种复杂的病症，涉及许多潜在的病理过程，包括兴奋性毒性和慢性炎症事件。本初步研究旨在探讨利拉鲁肽是否能减轻锂-匹罗卡品动物模型中SE诱导的慢性炎症反应和线粒体应激。我们发现，在SE诱导后每天一次腹腔注射25nmol/kg，持续7天的治疗可减轻慢性炎症，表现为海马中活化小胶质细胞和星形胶质细胞数量减少，以及TNF-α和IL-1β水平降低。利拉鲁肽可降低线粒体应激标志物BAX，并增强存活因子Bcl-2。利拉鲁肽对血糖水平无影响。我们首次表明，利拉鲁肽可减轻SE诱导的慢性炎症和线粒体应激，结果表明，像利拉鲁肽这样的GLP-1受体激动剂在SE后脑内具有修复和保护作用，可作为一种潜在的治疗方法。
