The Activation Of MTOR Signaling And Protective Role Of Rapamycin After Intracerebral Hemorrhage

Background:Mammalian target of rapamycin (mTOR) plays an vital role in cell proliferation and activation in many physiological and pathological activities. Here, we aimed to explore the activation timecourse of mTOR pathway and rapamycin’s role on neuron in ICH model.Methods:In this study,100 SD rats were divided into control group, ICH groups(6h, 24h,72h) and rapamycin group (24h ICH group treated by rapamycin). Western blot and immunofluorescence were used to detecte the activation of mTOR. Proteins p70S6K and 4EBP1, the downstream proteins of mTOR signal, were quautified with Western blot. The inflammatory factors TNF-α and IL-1β were valued with ELISA. Neuron injury was assessed by Nissl stain and TUNEL. Then, the neurological severity score was applied to evaluate the neurological function. Rapamycin was administrated i.p at 150ug/kg after the induction of ICH immediately, and the brain samples were extracted at 24h after ICH, which group is proved the maximum mTOR activation in experiment.Results:Our results demonstrated the protein level of mTOR pathway were significantly increased and peaked at 24h after ICH. Rapamycin markedly decreased the activation of mTOR pathway. In addition, administration of rapamycin following ICH significantly ameliorated neuron injury in perohemotoma region.Conclusions:Our findings suggested that the rapamycin may essentially attenuate neuron injury in this ICH model, possibly through inhibiting the activation of microglia by mTOR pathway.