Exploring Liraglutide in Lithium-Pilocarpine-Induced Temporal Lobe Epilepsy Model in Rats: Impact on Inflammation,...

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Glucagon-like peptide-1 receptor agonists (GLP-1RAs) like liraglutide exhibit neuroprotective properties in neurodegenerative diseases.
• The therapeutic potential of GLP-1RAs in temporal lobe epilepsy (TLE) is not well-established.

Purpose of the Study:

• To investigate the effects of liraglutide on inflammation, oxidative stress, and mitochondrial dynamics in a rat model of TLE.
• To evaluate the impact of liraglutide on cognitive and behavioral outcomes in TLE.

Main Methods:

• TLE was induced in rats using lithium chloride-pilocarpine hydrochloride.
• Liraglutide's effects on inflammatory markers (NLRP3, Caspase-1, IL-1β), antioxidant pathways (Nrf-2), and mitochondrial proteins (Pink1, Mfn2, Drp1) were assessed in hippocampal tissue via Western blot.
• Mitochondrial function in peripheral blood mononuclear cells (PBMCs) and cognitive-behavioral changes were evaluated.

Main Results:

• Liraglutide modulated NLRP3-mediated inflammation and reduced oxidative stress by activating Nrf-2 pathways in epileptic rats.
• Treatment restored levels of mitochondrial dynamics proteins (Pink1, Mfn2, Drp1) and altered PBMC mitochondrial function.
• Liraglutide reversed epilepsy-induced hyperactivity and improved cognitive-behavioral outcomes.

Conclusions:

• Liraglutide demonstrates significant anti-inflammatory, antioxidant, and neuroprotective effects in TLE.
• The drug positively influences mitochondrial dynamics and function in both brain and periphery.
• GLP-1RAs represent a promising therapeutic avenue for managing TLE.