Investigation Of The Multiple Brain Protective Effects Of Combined Edaravone And Minocycline On Cerebral Infarction

Objective To investigate the multiple-brain-protective effects of combined edaravone and minocycline on ischemia-reperfusion(I-R) injury treated with urokinase(UK) in rats,and investigate the delayed reperfusion treatment under the condition of multiple-brain-protection.Methods Male sprague-Dawley(SD) rats were subjected to middle cerebral artery occlusion(MCAO) by the intraluminal suture method.Parts of rats were divided into Sham,UK,UK+ED,UK+MC,UK+ED+MC groups.The infarct volume of brain was investigated by TTC coloring,the proliferation of microglia(MC) and the expression of poly(ADP ribose) polymerase-1(PARP-1) were analyzed by immunohistochemistry,the volume of bleeding,the level of myeloperoxidase(MPO) and malonaldehyde(MDA) were quantified with a spectrophotometer method.The otherpartincluded:2hUK,4.5hUK,4.5hUK+ED,4.5hUK+MC,4.5hUK+ED+MC,4.5hED+MC groups,and the infarction volume and bleeding volume were quantified in a way mentioned above.Results The relative stable infarction and bleeding volume and the notable increases of the expression of Isolectin B4(IB4) and PARP-1,and the level of MPO and MDA were seen in UK group. Among the comparison of infarction and bleeding volume and PARP pression between UK and NS groups, just only bleeding volume significantly increased in UK group. In MC or ED treatment group, the outcome parameters were attenuated,and they were more notablely attenuated in MC+ED group. In addition,compared to 2h UK group,delayed recanalization elevated both the infarction volume and bleeding volume which were reduced by ED or MC treatment and more significant impairment were seen in 4.5hUK+MC+ED group.At last, 4.5hUK+MC+ED group also has smaller infarction volume than MC+ED group(P< 0.05).Conclusion The combination therapy of edaravone(ED) with minocycline(MC) which showed more excellent effects on brain-protective through synergistic inhibition effects on free radical,inflammation and PARP-1 injury produced by I-R and UK,as smaller infarction and bleeding volume were seen in ED+MC group when compared to ED or MC group.Furthermore,in MCAO rats,the multiple-protection was able to expand the thrombolytic time window to 4.5h,and its therapeutic efficacy was not only better than single protection but also better than brain protection group without recanalization,which demonstrated the feasibility and necessary of delayed thrombolysis.