Metformin Attenuates Ferroptosis and Promotes Functional Recovery of Spinal Cord Injury

Abstract

Ferroptosis is involved in traumatic spinal cord injury (SCI), and its inhibition may improve functional recovery after traumatic SCI. This study investigated whether metformin (Met) can have a neuroprotective effect in SCI repair by inhibiting ferroptosis. We assessed functional change to determine the long-term effects after intraperitoneal injection of Met in SCI rats with the Basso-Beattie-Bresnahan locomotor rating scale. Malondialdehyde level and relative expression of key proteins, inflammatory cytokines, and nuclear factor E2-related factor 2 signalling molecules were determined in SCI rats and PC12cells exposed to FeCl3 solution. Met treatment decreased the contents of malondialdehyde, regulated the levels of inflammatory factors, activated the nuclear factor E2-related factor 2 signalling pathway, and improved long-term outcomes by ameliorating SCI-induced locomotor deficits. Invitro studies further confirmed the beneficial and antiferroptotic actions of Met partly through activation of nuclear factor E2-related factor 2 signalling. Met can have a neuroprotective effect on SCI repair partly through antiferroptotic effects.