Mtorc1 Pathway Disruption Ameliorates Brain Inflammation Following Stroke Via A Shift In Microglia Phenotype From M1 Type To M2 Type
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 thatmTORC1 signaling plays in poststroke neuroinflammation is not clear. To explore the relationship betweenmicroglial 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 ofmicroglia. For that purpose,we generated mice deficient in the regulatory associated protein ofmTOR(Raptor) inmicroglia,whosemTORC1signalingwas blocked, by crossing Raptor loxed (Raptorflox/flox)mice with CX3CR1CreER mice, 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 ofM1 type microglia. Thus, mTORC1 blockade apparently attenuated behavioral deficits and poststroke inflammation after middle cerebral artery occlusion by preventingmicroglia polarization toward theM1 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 fromM1 type toM2 type.
Digital Object Identifier (DOI)
Li, Daojing; Wang, Chunjiong; Yao, Yang; Chen, Li; Liu, Guiyou; Zhang, Rongxin; Liu, Qiang; Shi, Fu Dong; and Hao, Junwei, "Mtorc1 Pathway Disruption Ameliorates Brain Inflammation Following Stroke Via A Shift In Microglia Phenotype From M1 Type To M2 Type" (2016). Neurobiology. 162.