Elamipretide reduces pyroptosis and improves functional recovery after spinal cord injury

Abstract

AbstractAimsElamipretide (EPT), a novel mitochondria‐targeted peptide, has been shown to be protective in a range of diseases. However, the effect of EPT in spinal cord injury (SCI) has yet to be elucidated. We aimed to investigate whether EPT would inhibit pyroptosis and protect against SCI.MethodsAfter establishing the SCI model, we determined the biochemical and morphological changes associated with pyroptosis, including neuronal cell death, proinflammatory cytokine expression, and signal pathway levels. Furthermore, mitochondrial function was assessed with flow cytometry, quantitative real‐time polymerase chain reaction, and western blot.ResultsHere, we demonstrate that EPT improved locomotor functional recovery following SCI as well as reduced neuronal loss. Moreover, EPT inhibited nucleotide‐binding oligomerization domain‐like receptor 3 (NLRP3) inflammasome activation and pyroptosis occurrence and decreased pro‐inflammatory cytokines levels following SCI. Furthermore, EPT alleviated mitochondrial dysfunction and reduced mitochondrial reactive oxygen species level.ConclusionEPT treatment may protect against SCI via inhibition of pyroptosis.