Post-treatment with the GLP-1 analogue liraglutide alleviate chronic inflammation and mitochondrial stress induced by Status epilepticus

Abstract

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.

Keywords: Apoptosis; GLP-1; Inflammation; Insulin; Liraglutide; Neuroprotection.