Dopamine inhibits pyroptosis and attenuates secondary damage after spinal cord injury in female mice

•Dopamine suppresses NLRP3 inflammasome activation and pyroptosis.•Dopamine attenuates neuroinflammation.•Dopamine alleviates secondary damage. An excessive inflammatory response accompanies the pathogenesis of spinal cord injury (SCI) and has been found to be promoted by inflammasomes in a variety of disease models. Dopamine is a neurotransmitter that also regulates nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome-dependent neuroinflammation. However, little is known regarding the effects and molecular mechanisms underlying the role of dopamine in SCI. Functional recovery in mice was assessed with the Basso Mouse Scale (BMS). Neuronal loss was evaluated with immunochemical staining of NeuN. Pyroptosis was assessed with immunofluorescence staining, flow cytometry, western blotting, and cell viability and cytotoxicity assays. Dopamine was significantly associated with enhanced locomotor recovery after SCI, and with decreased NLRP3 inflammasome activation, pyroptosis, neuronal loss and pro-inflammatory cytokine levels. In vitro data suggested that dopamine suppressed NLRP3 inflammasome activation and pyroptosis, and decreased pro-inflammatory cytokine levels. Conclusions: Dopamine may be a novel approach for alleviating secondary damage after SCI.