Metformin Protects Against Spinal Cord Injury by Regulating Autophagy via the mTOR Signaling Pathway

Spinal cord injury (SCI) is a serious central trauma, leading to severe dysfunction of motor and sensory systems. Secondary injuries, such as apoptosis and cell autophagy, significantly impact the motor function recovery process. Metformin is a widely used oral anti-diabetic agent for type 2 diabetes in the world. It has been demonstrated to promote autophagy and inhibit apoptosis in the nervous system. However, its role in recovery following SCI is still unknown. In this study, we determined that motor function, assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor assessment scale, was significantly higher in rats treated with metformin following injury. Nissl staining revealed that metformin also increased the number of surviving neurons in the spinal cord lesion. Western blot and immunofluorescent analysis revealed that mammalian target of rapamycin (mTOR) and P70S6 kinase (P70S6K) decreased, while the expression of autophagy markers increased and apoptosis markers declined in animals treated with metformin following SCI. Taken together, these findings suggest that metformin functions as a neuroprotective agent following SCI by promoting autophagy and inhibiting apoptosis by regulating the mTOR/P70S6K signaling pathway.