Dopamine D1 Receptor Agonist A-68930 Inhibits NLRP3 Inflammasome Activation, Controls Inflammation, and Alleviates Histopathology in a Rat Model of Spinal Cord Injury.

Abstract

A randomized experimental study. The aim of this study was to investigate the therapeutic efficacy and molecular mechanisms of dopamine D1 receptor agonist A-68930 in spinal cord injury (SCI) rats. The inflammation induced by SCI includes maturation and secretion of pro-inflammatory cytokines interleukin (IL)-1β and IL-18 mediated by nucleotide-binding domain -like receptor protein 3 (NLRP3) inflammasome. Dopamine D1 receptor agonist A-68930 has been reported to exert neuroprotective effect via suppressing NLRP3 inflammasome activation in some central nervous injury models. However, whether A-68930 can exert nueroprotection in rat SCI models through inhibition of NLRP3 inflammasome activation has yet to be investigated. Eighty female Sprague-Dawley rats were randomly divided into 4 groups: sham group, SCI group, SCI + Vehicle (Veh) group, SCI + A-68930 group. The influences of A-68930 on the proinflammatory cytokines levels, histological changes, and locomotion scale were estimated. SCI significantly promoted NLRP3 inflammasome activation and increased proinflammatory cytokines productions in SCI group as compared with sham group. A-68930 administration significantly inhibited NLRP3 inflammasome activation and reduced inflammatory cytokines levels. Moreover, A-68930 administration attenuated histopathology and promoted locomotion recovery. A-68930 can attenuate tissue damage and improve neurological function recovery, and the mechanism may be related to the inhibition of NLRP3 inflammasome activation.