The Effects And Mechanism Of Valproic Acid In The Activation Of NLRP1/3 Inflammasome In Acute Spinal Cord Injury Rat

Background:Emerging studies have demonstrated that valproic acid(VPA)can promote the recovery after spinal cord injury(SCI)by different pathophysiological pathway.However,the effect of VPA on inflammasomes after spinal cord injury(SCI)remain unknown.Methods:We employed a SCI rat model in this study.Basso-Beattie-Bresnahan(BBB)locomotion scaling was conducted to evaluated the effect of VPA on treating spinal cord injury.HE staining and Evans blue staining were performed to evaluated the effect of VPA against SCI.Using western blot analysis and ELISA to investigate the mechanism of the suppression of infammasomes by VPA.Results:We found the functional recovery of SCI rats which accepted VPA treatment increased significantly compared with that of SCI rats without VPA treatment.This phenomenon demonstrated that VPA plays a neuroprotective role in post-SCI functional recovery.In addition,the administration of VPA could alleviate inflammatory exudation at the site of injury through HE staining.VPA could also protect blood spinal cord barrier in the Evans blue staining.Furthermore,western-blot analysis was exerted to clarify that VPA attenuates the levels of P2X7,NLRP3 inflammasome and NLRP1 inflammasome.Moreover,we found that IL-1 β and IL-18 was reduced in VPA group compared with that in SCI group.Conclusions:Our results demonstrate that VPA can improve functional recovery,reduce neuroinflammation and suppress the activation of NLRP1 and NLRP3 inflammasomes after SCI.The data indicate that the suppression of inflammasomes by VPA may be related with p2x7.