Potential Medications or Compounds Acting on Toll-like Receptors in Cerebral Ischemia

Abstract

Background: Toll-like receptors play an integral role in the process of inflammatory response after ischemic in-jury. The therapeutic potential acting on TLRs is worth of evaluations. The aim of this review was to introduce readers some potential medications or compounds which could alleviate the ischemic damage via TLRs.Methods: Research articles online on TLRs were reviewed. Categorizations were listed according to the follows, methods acting on TLRs directly, modulations of MyD88 or TRIF signaling pathway, and the ischemic tolerance induced by the pre-conditioning or postconditioning with TLR ligands or minor cerebral ischemia via acting on TLRs.Results: There are only a few studies concerning on direct effects. Anti-TLR4 or anti-TLR2 therapies may serve as promis-ing strategies in acute events. Approaches targeting on inhibiting NF-κB signaling pathway and enhancing interferon regu-latory factor dependent signaling have attracted great interests. Not only drugs but compounds extracted from traditional Chinese medicine have been used to identify their neuroprotective effects against cerebral ischemia. In addition, many re-searchers have reported the positive therapeutic effects of preconditioning with agonists of TLR2, 3, 4, 7 and 9. Several trails have also explored the potential of postconditioning, which provide a new idea in ischemic treatments. Considering all the evidence above, many drugs and new compounds may have great potential to reduce ischemic insults.Conclusion: This review will focus on promising therapies which exerting neuroprotective effects against ischemic injury by acting on TLRs.

Emodin Attenuates Lipopolysaccharide-Induced Acute Liver Injury via Inhibiting the TLR4 Signaling Pathway in vitro and in vivo

“…Then, LPS activates TLR4, which can initiate downstream signals via two main transduction signaling branches, myeloid differentiation factor88 (MyD88) and TIR-domain-containing adapter-inducing interferon-β (TRIF; Chattopadhyay et al, 2015 ; Wang, 2015 ). The TLR4 signaling pathway, via the two distinct branches of the MyD88- and TRIF-dependent pathways, activates the translocation of nuclear factor-kappa B (NF-κB) into the nucleus ( Khan et al, 2016 ; Singh et al, 2017 ; Li et al, 2018 ). Both of these pathways play critical roles in the expression of a series of inflammatory factors, including tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 ( Ben et al, 2012 ; Hwang et al, 2017 ).…”

Poly(I:C) preconditioning ameliorates cognitive dysfunction after cerebral I/R injury by inhibiting TRAF6 signaling

“…In this study, we employed a mouse model of MCAO to evaluate the effects of poly(I:C) preconditioning on cognitive dysfunction after cerebral I/R injury and the related mechanisms. We Recent studies have indicated that TLR-mediated signaling plays an important role in cerebral I/R injury [4,32]. TLR4 deficiency [5] or TLR2 modulation [33] protects the brain from I/R injury.…”

Effects of TLR3 and TLR9 Signaling Pathway on Brain Protection in Rats Undergoing Sevoflurane Pretreatment during Cardiopulmonary Bypass

“…TLR9 signaling pathway, as an important hinge between innate immunity and acquired immunity, can play an immune regulatory role in the early stage of pathogen invasion [ 39 ]. In ischemic brain injury, TLR9 activates the downstream signaling molecule NF- κ B by binding to specific ligands and participates in inflammatory response [ 40 ]. Trop et al [ 41 ] found that CPB increased inflammatory response, induced high expression of interferon-gamma (INF- γ ), TNF- α , IL-6, IL-8, and IL-10, activated TLRs signaling pathway, and upregulated IRAK-4 and NF- κ B expression.…”