Abstract Sepsis-induced encephalopathy (SAE) affects about 70% of patients with sepsis and therefore leads to poor prognosis and long-term cognitive dysfunction. Unfortunately, there are still no effective pharmacological treatments to better manage this kind of encephalopathy. Recently, glucagon-like peptide 1 receptor (GLP-1R) agonists have gained much attention due to their neuroprotective effects in neurodegenerative diseases and brain injuries. In this study, we evaluated the potential effects of intracerebroventricular injection of Liraglutide, a kind of GLP-1R agonists, in SAE mice. We found that Liraglutide injected via intracerebroventricular improved neurological deficits and attenuated neuronal loss and degeneration, and glial cell activations in the hippocampus of septic mice. In vitro studies demonstrated that Liraglutide inhibited the interaction between microglia and neurons under LPS stimulation. Furthermore, Liraglutide restrained oxidative distress and mitochondria damage in hippocampal neurons. Mechanically, Liraglutide restored the downregulation of p-AKT but reversed the phosphorylation of STAT3 in hippocampal neurons. Collectively, these results indicated that the administration of GLP-1R agonist Liraglutide might exert neuroprotective effects on sepsis-induced brain impairments.
Yi et al. (Wed,) studied this question.