Everolimus attenuated ischemic injury caused by middle cerebral artery obstruction in rat

Background and Aim : Evaluation of the effects of everolimus (a potent and selective inhibitor of mammalian target of rapamycin, mTOR) on the neuronal damage due to middle cerebral artery (MCA) occlusion, as a focal cerebral ischemia model in rat.Methods : Rats were randomly divided into 4 groups; each contains 8 rats. In the sham group, surgery was performed without ischemia induction. In the control group, ischemia-reperfusion injury was induced by transient ligation of the middle cerebral artery for 30 min, followed by reperfusion for 24 hours (MCAO). In the treatment groups, Everolimus (1 mg/kg and 5 mg/kg) was administrated at the time of reperfusion, intraperitoneally. After that, the neurologic function was evaluated using rotarod apparatus. The extent of the ischemic region, histologic changes, and the level of oxidative stress were assessed using TTC, H & E staining methods and levels of hippocampal glutathione or lipid peroxidation, respectively.Results : MCA obstruction leads to regional ischemia and also significant increase in the oxidative markers, as compared with sham group (p<0.001). Everolimus significantly reduced the infarction volume, cellular injury and lipid peroxides (p<0.01 and p<0.001, respectively) and also significantly increased the latency on rod (p<0.001) and tissue glutathione level (p<0.05).Conclusion : Everolimus dose-dependently protected against cerebral ischemia-reperfusion injury induced by MCAO, by means of attenuating oxidative stress.

Keywords:

Everolimus , Mammalian target of rapamycin (mTOR) , Middle cerebral artery occlusion (MCAO) , Cerebral ischemia-reperfusion injury , Oxidative stress