Background: 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.
Methods: 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 PC12 cells exposed to FeCl3 solution.
Results: 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. In vitro studies further confirmed the beneficial and antiferroptotic actions of Met partly through activation of nuclear factor E2-related factor 2 signalling.
Conclusion: Met can have a neuroprotective effect on SCI repair partly through antiferroptotic effects.
Keywords: Ferroptosis; Inflammation; Metformin; Neuroprotection; Spinal cord injury.
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