Liraglutide alleviates sepsis-associated encephalopathy via attenuating neuronal damage, glial cell activation and mitochondrial dysfunction in a mouse model of sepsis.

OBJECTIVE: To explore the relevant mechanisms and principles by which liraglutide alleviates sepsis-associated encephalopathy (SAE) through reducing neuronal injury, glial cell activation and mitochondrial dysfunction. METHODS: Adult male C57BL/6 J mice were included in this study. C57BL/6 J mice were randomly divided into three groups: cecal ligation and puncture (CLP) group, CLP + liraglutide group, and sham operation group. One hour before CLP, mice in each group were treated with PBS or intracerebroventricular (i.c.v.) liraglutide. On the day after CLP, the brains of the mice were removed for immunohistochemistry, transmission electron microscopy, and Western blot analysis. Modified neurological severity scores were performed on the mice at 0, 1, 3, and 5 days after CLP surgery. The weight loss and food intake and survival rate of the animals in each group were monitored until euthanasia. In vitro experiments used BV2 and HT22 cells to detect the migration of BV2 cells. RESULTS: This study assessed the potential neuroprotective impacts of i.c.v. administration of Liraglutide, a glucagon-like peptide 1 receptor (GLP-1R) agonist, in septic mice. Liraglutide administered intracerebroventricularly alleviated neurological impairments and reduced glial cell activations, neuronal loss, as well as degeneration in the hippocampal regions of septic mice. Liraglutide was shown in vitro to suppress the interaction between neurons and microglia when the cells were stimulated with LPS. Liraglutide also inhibited mitochondrial damage and oxidative stress in hippocampus neurons. Mechanistically, Liraglutide restored the diminished p-AKT levels while simultaneously reversing STAT3 phosphorylation in hippocampal neurons. CONCLUSION: GLP-1R agonist Liraglutide may have neuroprotective properties on SAE.