Neuroprotective effects of exendin-4 in rat model of spinal cord injury via inhibiting mitochondrial apoptotic pathway.

Abstract

Spinal cord injury (SCI) is a devastating problem of health. Glucagon-like peptide-1 (GLP-1) is glucose-dependent insulinotropic hormone. Exendin-4 is the longacting GLP-1 receptor agonist that used as an anti-diabetic drug. Recent studies demonstrated exendin-4 has a series of beneficial neuroprotective properties. This study was designed to assess the neuroprotective effects of exendin-4 against spinal cord injury. 72 rats were randomly divided into three groups as follows: sham operation group, SCI group, and exendin-4 group (intraperitoneal injection of exendin-4 at 10 μg/rat immediately after SCI). First, a decrease of malodialdehyde (MDA) levels and an increase of glutathione (GSH) levels in the exendin-4 group demonstrated the anti-oxidation effect of exendin-4. Further, the preservation of mitochondrial membrane potential (ΔΨm) and the reduction of cytochrome c release suggested the protection for mitochondria. Moreover, a decline of the expression level of Bax, Bcl-2 and caspase-3 and the results of TUNEL staining indicated its anti-apoptosis role. Finally, behavioral assessment with Basso Beattle Bresnahan locomotor rating scale (BBB) showed that animals in exendin-4 group achieved a significant increase in BBB scores. Our results suggest that exendin-4 prevents against SCI-induced mitochondrial apoptotic pathway and contributes to functional improvement after SCI.