Effects of GLP-1 Receptor Agonist Exenatide on Mitochondrial Dysfunction After Spinal Cord Injury

Spinal cord injury (SCI) triggers secondary pathological processes, including inflammation, oxidative stress, and mitochondrial dysfunction, that contribute to progressive neuronal damage. Because mitochondria play a central role in cellular homeostasis, mitochondrial impairment is considered an important component of SCI pathophysiology. We investigated the effects of exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, on mitochondrial dysfunction after SCI using a rat contusion model and C6 glioma cells. Exenatide was associated with increased OPA1 expression and enhanced Drp1 phosphorylation at Ser637, suggesting a shift in mitochondrial dynamics toward fusion-dominant regulation. Exenatide also tended to increase the expression of Bcl-2, HO-1, and p62. In vitro, exenatide attenuated H₂O₂- and CCCP-induced reductions in cell viability, preserved mitochondrial membrane potential, and reduced the proportion of dead cells. These findings suggest that exenatide may mitigate secondary injury after SCI in association with mitochondrial protective responses.