Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8274096 | Journal of the Neurological Sciences | 2016 | 8 Pages |
Abstract
Here, we aimed to study the role and underlying mechanism of mTOR in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Experiment 1, the time course of mTOR activation in the cortex following SAH. Experiment 2, the role of mTOR in SAH-induced EBI. Adult SD rats were divided into four groups: sham group (n = 18), SAH + vehicle group (n = 18), SAH + rapamycin group (n = 18), SAH + AZD8055 group (n = 18). Experiment 3, we incubated enriched microglia with OxyHb. Rapamycin and AZD8055 were also used to demonstrate the mTOR's role on microglial polarization in vitro. The phosphorylation levels of mTOR and its substrates were significantly increased and peaked at 24 h after SAH. Rapamycin or AZD8055 markedly decreased the phosphorylation levels of mTOR and its substrates and the activation of microglia in vivo, and promoted the microglial polarization from M1 phenotype to M2 phenotype. In addition, administration of rapamycin and AZD8055 following SAH significantly ameliorated EBI, including neuronal apoptosis, neuronal necrosis, brain edema and blood-brain barrier permeability. Our findings suggested that the rapamycin and AZD8055 could attenuate the development of EBI in this SAH model, possibly through inhibiting the activation of microglia by mTOR pathway.
Keywords
p70S6KaSAH4EBP1EBISAHmTORC1IPCPI3KCBFPMSFTSCRAPA4E binding protein 1mTORICPPVDFmTOR complex 1Early brain injurySprague-Dawleyinflammationcerebral blood flowSubarachnoid hemorrhageAneurysmal subarachnoid hemorrhageCNSpolyvinylidene difluorideRapamycinBBBcentral nervous systemphenylmethylsulfonyl fluorideMicroglia polarizationBlood-brain barriermammalian target of rapamycinischemic postconditioningTuberous sclerosis complex
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Authors
Wanchun You, Zhong Wang, Haiying Li, Haitao Shen, Xiang Xu, Genlai Jia, Gang Chen,