Neuroprotective effect of edaravone dexborneol in rats with acute permanent focal cerebral ischemia via inhibiting NLRP3
HUANG Tengyue
ZHANG Yanhai
LIU Litian
CHANG Linli
BAI Wanqi
ZHAO Hongyi
CHI Liyi
Abstract：Objective To investigate the neuroprotective effects of free radical scavenger edaravone and bicyclic monoterpenoid dexborneol on the injury of acute ischemic stroke(AIS)and their effects and mechanism on NLRP3 inflammasome in microglia.Methods The experimental animals were randomly divided into 5 groups(n=10):①Sham group;②middle cerebral artery occlusion(MCAO)group;③1.5 h group;④3.0 h group;⑤4.5 h group.A rat model of MCAO was established using the thread embolism method,and MCAO rats were treated with edaravone dexborneol(EDB)to evaluate the nervous system status of the rats.The cerebral infarction volume was measured through TTC staining.The nerve cell apoptosis was observed by Nissl staining and TUNEL staining.The expression levels of CD68,Iba-1 and Arg-1 were analyzed by immunofluorescence,and NLRP3,Caspase-1,C-Caspase-1,IL-1β,and other key molecules were detected by Western blotting.Results At 24 h after infarction,EDB injection improved the volume of focal infarction in the brain tissue of MCAO rats(MCAO group vs 1.5 h group,P=0.000 2;MCAO group vs 3.0 h group,P=0.014 3),alleviated nerve cell injury and apoptosis(MCAO group vs 1.5 h group,P＜0.000 1;MCAO group vs 3.0 h group,P=0.000 3;MCAO group vs 4.5 h group,P=0.003 0),decreased the expression of NLRP3 inflammatosome(MCAO group vs 1.5 h group,P=0.006 1)and its downstream proteins Caspase-1(MCAO group vs 1.5 h group,P=0.001 2;MCAO group vs 3.0 h group,P=0.006 2;MCAO group vs 4.5 h group,P=0.025 6),C-Caspase-1,and IL-1 β(MCAO group vs 1.5 h group,P=0.037 4),decreased the expression of microglial marker Iba-1(MCAO group vs 1.5 h group,P=0.000 8;MCAO group vs 3.0 h group,P=0.030 3)and activated microglial marker CD68(MCAO group vs 1.5 h group,P＜0.000 1;MCAO group vs 3.0 h group,P=0.000 3;MCAO group vs 4.5 h group,P=0.000 7),and decreased the expression of M1 and M2 in neuroinflammatory response(MCAO group vs 1.5 h group,P=0.000 2;MCAO group vs 3.0 h group,P=0.006 1).Conclusion EDB can slow down microglial activation and significantly ameliorate the neuroinflammatory response by effectively blocking NLRP3.EDB injection group at 1.5 h is better than EDB injection group at 3.0 h and 4.5 h.However,the transformation of microglia from M1 to M2 phenotype is not obvious in the early stage.
Keywords：strokeedaravone dexborneolmicrogliaNLRP3 inflammasome
Publication Date：2025-03-31
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：7( 292-298 )