Rapamycin Pretreatment Alleviates Cerebral Ischemia/Reperfusion Injury in Dose-Response Manner Through Inhibition of the Autophagy and NFκB Pathways in Rats

Abstract

Although rapamycin can attenuate cerebral ischemia/reperfusion (I/R) injury, the potential roles of rapamycin on cerebral I/R injury remain largely controversial. The present work aims to evaluate underlying molecular mechanisms of rapamycin pretreatment on I/R injury. In total, 34 Sprague-Dawley rats were randomly grouped to 3 groups: sham group (n = 2), vehicle group (n = 16), and rapamycin-pretreatment group (n = 16). Before the focal cerebral ischemia was induced, those rats in the pretreatment group were intraperitoneally injected rapamycin (1 mg/kg body) for 20 hours, while rats in the vehicle group received same-volume saline. Then, rats in these 2 groups received focal cerebral ischemia for 3 and 6 hours, respectively (n = 8 in each group), which was followed by the application of reperfusion for 4, 24, 72 hours, and 1 week (n = 2 in each group). The results showed that the rapamycin pretreatment improved the memory functions of rats after I/R injury, which was evaluated using a Y-maze test. Rapamycin pretreatment significantly reduced the size of triphenyltetrazolium chloride infarction and decreased the expression of I/R injury markers. Moreover, the expression of LC-3 and NFκB was also significantly reduced after rapamycin pretreatment. Taken together, rapamycin pretreatment may alleviate cerebral I/R injury partly through inhibiting autophagic activities and NFκB pathways in rats.