RETRACTED: 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.

Resveratrol attenuates autophagy and inflammation after traumatic brain injury by activation of PI3K/Akt/mTOR pathway in rats

“…Erlich et al [8] showed that rapamycin, which induces neuronal autophagy by inhibiting its' mammalian target protein, improved neurological prognosis after TBI. On the other hand, accumulating evidence suggests that the activation of the neuronal autophagy pathway is related to the pathological mechanism of post-traumatic brain injury, and inhibition of this pathway can alleviate brain injury and functional defects [10,15,21]. In our current study, treatment with resveratrol suppressed the expression levels of LC3 II and Beclin-1, and increased P62 in the hippocampus at 12, 24, and 48 hours after injury.…”

EGCG protects the mouse brain against cerebral ischemia/reperfusion injury by suppressing autophagy via the AKT/AMPK/mTOR phosphorylation pathway

“…Basal autophagic activity exists in cells under physiological conditions, while the process turns more active induced by various stress events including CIRI and plays complex roles ( Wirawan et al, 2012 ). Some studies demonstrated that the activation of autophagy ameliorated CIRI ( Sun et al, 2020b ; Xu et al, 2020 ; Zhang B. et al, 2020 ; Chen et al, 2021 ; Jin et al, 2021 ; Yihao et al, 2021 ; Zha et al, 2021 ), while more research supported that the inhibition of autophagy activation exerted a neuroprotective effect in brain stroke ( Sun et al, 2020a ; Zhang et al, 2020b ; Li and Huang, 2020 ; Mei et al, 2020 ; Shi et al, 2020 ; Wang L. et al, 2020 ; Gu et al, 2021 ; Liu N. et al, 2021 ; Shao et al, 2021 ; Wang C. et al, 2021 ; Xu et al, 2021 ; Yao et al, 2021 ; Zhang et al, 2021 ; Zhao et al, 2021 ). Obviously, the controversial dual role of the induction of autophagy in the ischemic brain is still a hot topic in research and remains to be further investigated.…”

Activation of moderate autophagy promotes survival of fat graft

“…In an early study, rapamycin has been confirmed to promote tumor cell apoptosis by promoting autophagy. [32][33][34] However, several studies reported that rapamycin can reduce ischemia-reperfusion injury, [35][36][37] delay cell senescence, and prolong the lifespan. [38][39][40] As reported by a recent study, ADSCs pretreated by rapamycin can further promote the angiogenesis and survival of fat grafts.…”