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

Abstract

Toll-like receptors (TLRs) have been suggested to play an integral role in the process of inflammatory response after ischemic injury. Amongst all 9 TLRs present in the brain, functions of TLR2, TLR3, TLR4, TLR7, TLR8 and TLR9 have been studied in recent years. The MyD88 pathway and TIR domain-containing adaptor inducing interferon pathway are involved in these pathophysiological changes. For its important role, the therapeutic potential of strategies acting on TLRs needs further evaluation. Feasible approaches may function in the following respects, such as methods acting on TLRs directly, modulations of MyD88 or TRIF signaling pathway, and the ischemic tolerance induced by the preconditioning or post conditioning with TLR ligands or minor cerebral ischemia. There are only a few studies concerning direct effects. Anti-TLR4 or anti-TLR2 therapies may serve as promising strategies in acute events. Approaches such as targeting on inhibiting NF-kappaB signaling pathway and enhancing interferon regulatory factor dependent signaling have attracted great interests. Not only drugs but also compounds extracted from traditional Chinese medicine have been used to identify their neuroprotective effects against cerebral ischemia. In addition, many researchers 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 post conditioning, which provides a new idea in ischemic treatments. Considering all the evidence above, many drugs and new compounds may have great potential to reduce ischemic insults. This review will focus on promising therapies exerting neuroprotective effects against ischemic injury by acting on TLRs.