Elamipretide reduces pyroptosis and improves functional recovery after spinal cord injury

Spinal cord injury (SCI) causes disability and places a burden on individuals and society. This study investigates Elamipretide (EPT)'s potential to protect against SCI by inhibiting pyroptosis, a form of cell death contributing to inflammation and neuronal loss after SCI. The study uses in vivo (mice) and in vitro (cultured neurons) models of SCI to determine whether EPT can protect neurons, reduce inflammation, and prevent neuronal loss. The researchers also investigate the underlying mechanisms through which EPT might exert these effects. Researchers found that EPT improved locomotor functional recovery, reduced neuronal loss, inhibited NLRP3 inflammasome activation, decreased pro-inflammatory cytokines levels, and alleviated mitochondrial dysfunction, suggesting that EPT treatment may protect against SCI via inhibition of pyroptosis.

• 1
  EPT treatment led to a significant increase in NeuN-positive cells 28 days after SCI in EPT-treated animals, indicating reduced neuronal loss.
• 2
  EPT treatment significantly inhibited pyroptosis and attenuated neuroinflammation following SCI in mice, as shown by lower levels of GSDMD, GSDMD-N, IL-1β, and IL-18.
• 3
  EPT treatment significantly inhibits NLRP3 inflammasome activation in vivo and in vitro, suggesting that the mechanisms of suppression of pyroptosis by EPT after SCI depend on the attenuation of the NLRP3 inflammasome activation.