1. Academic Validation
  2. Inhibition of mammalian target of rapamycin attenuates early brain injury through modulating microglial polarization after experimental subarachnoid hemorrhage in rats

Inhibition of mammalian target of rapamycin attenuates early brain injury through modulating microglial polarization after experimental subarachnoid hemorrhage in rats

  • J Neurol Sci. 2016 Aug 15;367:224-31. doi: 10.1016/j.jns.2016.06.021.
Wanchun You 1 Zhong Wang 1 Haiying Li 1 Haitao Shen 1 Xiang Xu 1 Genlai Jia 2 Gang Chen 3
Affiliations

Affiliations

  • 1 Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China.
  • 2 Department of Neurosurgery, The People's Hospital of Rugao, Jiangsu, Rugao 226500, China.
  • 3 Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China. Electronic address: [email protected].
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 24h 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

Early brain injury; Inflammation; Mammalian target of rapamycin; Microglia polarization; Subarachnoid hemorrhage.

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