Anti-apoptotic and Neuroprotective Effects of the Antioxidant Edaravone in Rats Subjected to Cerebral Ischemia-Reperfusion Injury
Liping Bao
Abstract
Liping Bao
Abstract
Objective To study the antiapoptotic and neuroprotective effects of the antioxidant edaravone in rats with a model of ischemia-reperfusion injury. Methods 84 SD rats were randomly divided into groups:①the sham operation group(n=4),② ischemia-reperfusion(IR) group(n=40),and③edaravone treatment group(n=40).A model of cerebral ischemia-reperfusion injury was set up in each of the rats of groups② and group③ by suture-tying and untying the middle cerebral artery.Rats of group② and group③ were further divided into 2,6,12,24 and 48 hour subgroups according to the time of reperfusion.Rats of group③ were given each an IV injection of mg·kg-1 of edaravone following the 2 hour ischemia.24 h later a second injection of the same dose of edaravone was given to each of the rats of group③ by the same route.Rats of group③ were given each injections of equivalent amounts of physiologic saline solution at the same times and in the same manner as described above.The serum concentration of malonyldialdehydc(MDA) was determined with the colorimetric method.Bcl-2 immunohistochemical method and TUNEL staining were used to determine the expression of the bcl-2 protein and number of TUNEL-positive apoptotic cells in the brain tissue.The sizes of the brain infarction were assessed as well. Results After 6,12,24 and 48 hours of reperfusion,the sizes of brain infarction in rats of group③ treated with edaravone were obviously smaller than those in rats of group②(P0.05),and the serum MDA concentrations in rats of group③ were significantly lower than those in rats of group②(P0.05).In addition,there was an evident increase in the expression of bcl-2 protein(P0.01) and a striking decrease in the number of TUNEL-positive apoptotic cells in the brain tissue of the rats in group③ treated with edaravone as compared with those in rats of group② at the same time points(P0.01). Conclusion Edaravone was shown to have an excellent neuroprotective effect in rats subjected to an ischemia-reperfusion brain injury possibly by scavenging free radicals and a bcl-2 dependent anti-apoptotic mechanism.
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Objective To study the antiapoptotic and neuroprotective effects of the antioxidant edaravone in rats with a model of ischemia-reperfusion injury. Methods 84 SD rats were randomly divided into groups:①the sham operation group(n=4),② ischemia-reperfusion(IR) group(n=40),and③edaravone treatment group(n=40).A model of cerebral ischemia-reperfusion injury was set up in each of the rats of groups② and group③ by suture-tying and untying the middle cerebral artery.Rats of group② and group③ were further divided into 2,6,12,24 and 48 hour subgroups according to the time of reperfusion.Rats of group③ were given each an IV injection of mg·kg-1 of edaravone following the 2 hour ischemia.24 h later a second injection of the same dose of edaravone was given to each of the rats of group③ by the same route.Rats of group③ were given each injections of equivalent amounts of physiologic saline solution at the same times and in the same manner as described above.The serum concentration of malonyldialdehydc(MDA) was determined with the colorimetric method.Bcl-2 immunohistochemical method and TUNEL staining were used to determine the expression of the bcl-2 protein and number of TUNEL-positive apoptotic cells in the brain tissue.The sizes of the brain infarction were assessed as well. Results After 6,12,24 and 48 hours of reperfusion,the sizes of brain infarction in rats of group③ treated with edaravone were obviously smaller than those in rats of group②(P0.05),and the serum MDA concentrations in rats of group③ were significantly lower than those in rats of group②(P0.05).In addition,there was an evident increase in the expression of bcl-2 protein(P0.01) and a striking decrease in the number of TUNEL-positive apoptotic cells in the brain tissue of the rats in group③ treated with edaravone as compared with those in rats of group② at the same time points(P0.01). Conclusion Edaravone was shown to have an excellent neuroprotective effect in rats subjected to an ischemia-reperfusion brain injury possibly by scavenging free radicals and a bcl-2 dependent anti-apoptotic mechanism.
Key concepts: Edaravone, Medicine, Ischemia, Neuroprotection, Anesthesia, Reperfusion injury, TUNEL assay, Apoptosis