Function and mechanism of toll-like receptors in cerebral ischemic tolerance: from preconditioning to treatment.
Increasing evidence suggests that toll-like receptors (TLRs) play an important role in cerebral ischemia-reperfusion injury. The endogenous ligands released from ischemic neurons activate the TLR signaling pathway, resulting in the production of a large number of inflammatory cytokines, thereby causing secondary inflammation damage following cerebral ischemia. However, the preconditioning for minor cerebral ischemia or the preconditioning with TLR ligands can reduce cerebral ischemic injury by regulating the TLR signaling pathway following ischemia in brain tissue (mainly, the inhibition of the TLR4/NF-κB signaling pathway and the enhancement of the interferon regulatory factor-dependent signaling), resulting in TLR ischemic tolerance. Additionally, recent studies found that postconditioning with TLR ligands after cerebral ischemia can also reduce ischemic damage through the regulation of the TLR signaling pathway, showing a significant therapeutic effect against cerebral ischemia. These studies suggest that the ischemic tolerance mediated by TLRs can serve as an important target for the prevention and treatment of cerebral ischemia. On the basis of describing the function and mechanism of TLRs in mediating cerebral ischemic damage, this review focuses on the mechanisms of cerebral ischemic tolerance induced by the preconditioning and postconditioning of TLRs and discusses the clinical application of TLRs for ischemic tolerance.
Department of Neurology, Xinqiao Hospital & the Second Affiliated Hospital, the Third Military Medical University, No. 183, Xinqiao Main Street, Shapingba District, Chongqing, 400037, China. wpf5287598@163.com.|Department of Neurology, Weihai municipal Hospital, Weihai, 264200, China. wpf5287598@163.com.
Peng-Fei
PF
Wang
Department of Neurology, Xinqiao Hospital & the Second Affiliated Hospital, the Third Military Medical University, No. 183, Xinqiao Main Street, Shapingba District, Chongqing, 400037, China. xiongxy1989@hotmail.com.
Xiao-Yi
XY
Xiong
Department of Neurology, Xinqiao Hospital & the Second Affiliated Hospital, the Third Military Medical University, No. 183, Xinqiao Main Street, Shapingba District, Chongqing, 400037, China. 410752133@qq.com.
Jing
J
Chen
Department of Neurology, Xinqiao Hospital & the Second Affiliated Hospital, the Third Military Medical University, No. 183, Xinqiao Main Street, Shapingba District, Chongqing, 400037, China. wangyanchun86@163.com.
Yan-Chun
YC
Wang
Department of Neurology, Xinqiao Hospital & the Second Affiliated Hospital, the Third Military Medical University, No. 183, Xinqiao Main Street, Shapingba District, Chongqing, 400037, China. weiduantmmu@gmail.com.
Wei
W
Duan
Department of Neurology, Xinqiao Hospital & the Second Affiliated Hospital, the Third Military Medical University, No. 183, Xinqiao Main Street, Shapingba District, Chongqing, 400037, China. yangqwmlys@hotmail.com.
Qing-Wu
QW
Yang
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D051193:Toll-Like Receptors / Q000378:metabolism*
D016207:Cytokines; D051193:Toll-Like Receptors