title: mTORC1 pathway disruption ameliorates brain inflammation following stroke via a shift in microglia phenotype from M1 type to M2 type.
abstract: Inflammatory factors secreted by microglia play an important role in focal ischemic stroke. The mammalian target of rapamycin (mTOR) pathway is a known regulator of immune responses, but the role that mTORC1 signaling plays in poststroke neuroinflammation is not clear. To explore the relationship between microglial action in the mTORC1 pathway and the impact on stroke, we administered the mTORC1 inhibitors sirolimus and everolimus to mice. Presumably, disrupting the mTORC1 pathway after focal ischemic stroke should clarify the subsequent activity of microglia. For that purpose, we generated mice deficient in the regulatory associated protein of mTOR (Raptor) in microglia, whose mTORC1 signaling was blocked, by crossing Raptor loxed (Raptorflox/flox) mice with CX3CR1CreERmice, which express Cre recombinase under the control of the CX3C chemokine receptor 1 promoter. mTORC1 blockade reduced lesion size, improved motor function, dramatically decreased production of proinflammatory cytokines and chemokines, and reduced the number of M1 type microglia. Thus, mTORC1 blockade apparently attenuated behavioral deficits and poststroke inflammation after middle cerebral artery occlusion by preventing microglia polarization toward the M1 type.-Li, D., Wang, C., Yao, Y., Chen, L., Liu, G., Zhang, R., Liu, Q., Shi, F.-D., Hao, J. mTORC1 pathway disruption ameliorates brain inflammation following stroke via a shift in microglia phenotype from M1 type to M2 type.
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Daojing
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China.
authors.forename: Chunjiong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
authors.forename: Guiyou
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Immunology, Tianjin Medical University, Tianjin, China; and.
authors.forename: Rongxin
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China; Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China; Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
authors.forename: Fu-Dong
authors.initials: FD
authors.lastname: Shi
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China; hjw@tmu.edu.cn.
authors.forename: Junwei
authors.initials: J
authors.lastname: Hao
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism; D004195:Disease Models, Animal; D004660:Encephalitis / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D020521:Stroke / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: glia cells; ischemia; polarization