Neuroprotective Effect And Underlying Mechanisms Of SQ29548,a Thromboxane A2 Receptor Antagonist,on Ischemic Stroke-induced Damage

Background:Inflammatory response plays an important role in the process of cerebral infarction induced injury.Recently,it is clear that TXA2R exhibits a wide distribution in different cell types and new functions of TXA2R have been assigned in inflammation,immunity.However,the effect of TXA2R in ischemic stroke is unclear.Selective pharmacological modulation of the inflammatory response after cerebral infarction can improve neurological outcome and ameliorate brain injury.The present study explored whether TXA2R participated in cerebral infarction-induced inflammatory responses in the brain.Method:Adult male ICR mice underwent 90-min transient middle cerebral artery occlusion(tMCAO).SQ29548,a TXA2R antagonist,was administered to the ipsilateral ventricle after tMCAO.Cerebral infarction volume,inflammatory cytokines release and microglia/macrophages activation were measured using the cresyl violet method,quantitative polymerase chain reaction(qPCR),and immunofluorescence double staining and Western blotting,respectively.In the BV2 cell line,LPS-stimulated NO release,inflammatory cytokines release,and phosphorylation of MAPKs and NF-κB were assessed using a NO assay kit,qPCR and Western blot,respectively.Results:Expression of TXA2R was significantly increased in the ipsilateral brain tissue after ischemia/reperfusion.Administration of SQ29548 decreased infarction volume and improved neurological outcome after ischemia/reperfusion injury.In vitro studies demonstrated that SQ29548 inhibited LPS-stimulated BV2 activation and reduced the mRNA levels of IL-11β,IL-6,TNFa and iNOS through inhibition of MAPKs and the NF-κB signaling pathway.Conclusion:SQ29548(thromboxane A2 receptor antagonist)reduced ischemic brain injury.Background and Objective:Recent research on genome-wide associations has implicated that the serum resistin level and its gene polymorphism are associated with cerebral infarction(CI)morbidity and prognosis,and could thereby regulate CI.This study aimed to investigate the association between the resistin single nucleotide polymorphism(SNP)and the susceptibility to CI in the Chinese Han population.Methods:A total of 550 CI patients and 313 healthy controls were genotyped.Nine SNPs of the resistin gene previously shown were sequenced and assessed for an association with CI.Results:The numbers of GG genotype carriers of rs3219175 and rs3486119 in the CI group were significantly higher than those in the control group among the middle-aged group(aged 45-65),at 76%vs 67.9%(P=0.025)and 75.5%vs 67.9%(P=0.031).rs3219175 and rs34861192 were associated with CI in the dominant and superdominant models according to the genetic model analysis(P<0.05).Meanwhile,there was a strong linkage disequilibrium among the rs34124816,rs3219175,rs34861192,rs1862513,rs3745367,180C/G and rs3745369 sites.In a haplotype analysis,the occurrence rate of the haplotype AGGCAGC was 1.97 times(P<0.05)higher in the patient group than in the control group.In addition,the numbers of GG genotype carriers of rs3219175 and rs3486119 in the middle-aged male CI patients and the middle-aged small artery occlusion(SAO)CI patients were higher than those in the control group(P<0.05).Conclusion:In the Chinese Han middle-aged population,the GG gene type carriers of the resistin gene sites rs3219175 and rs34861192 had a high risk for CI onset,especially in middle-aged male patients and SAO CI in all middle-aged patients...