Therapeutic effect of metformin on inflammation and apoptosis after spinal cord injury in rats through the Wnt/β-catenin signaling pathway

Abstract

Objective: To verify the effect of metformin on spinal cord injury (SCI) through Wnt/β-catenin signaling pathway.

Background: SCI is a serious traumatic disease of the central nervous system. Wnt/β-catenin signaling pathway plays important roles in SCI. Metformin has been reported to exert neuroprotective effects in the central nervous system. Whether metformin could improve SCI through Wnt/β-catenin signaling pathway remains unclear.

Methods: Rats were divided into sham group, SCI group, SCI + metformin group, metformin + XAV939 group (XAV939 is an effective inhibitor of the Wnt/β-catenin signaling pathway), and methylprednisolone group. BBB scores were used to detect motor function recovery at different time points (0, 1, 3, 7, 14, 21, and 28 days) in SCI rats. Western blot analysis, immunofluorescence, TUNEL, HE and Nissl staining were used to observe the morphological characteristics of spinal cord tissue and the expression of inflammation and apoptosis in spinal cord neurons.

Results: Metformin(50 mg/kg) promoted motor functional recovery in rats after SCI, increased the expressions of β-catenin and brain derived neurotrophic factor (BDNF), inhibited neuron apoptosis and inflammatory response, and improved the recovery of pathological morphology at the injury site by activating the Wnt/β-catenin signaling pathway.

Conclusion: We found a possible mechanism that metformin could reduce inflammation and apoptosis, and promote functional recovery of SCI rats through activating Wnt/β-catenin signaling pathway.

Keywords: Inflammation; Metformin; Neuroprotection; Spinal cord injury; Wnt/β-catenin signaling pathway.