Toll-like receptors and tolerance to ischaemic injury in the brain.

Ischaemic tolerance in the brain is a powerful adaptive defence that involves an endogenous programme of neuroprotection culminating in marked protection against brain injury from ischaemia. A range of preconditioning stimuli exist that differ in ligand and target characteristics but share the common feature of causing mild stress or insult without inducing overt injury. The protective phenotype that emerges confers tolerance to subsequent exposure to injurious insults. Tolerance to injury is the result of genomic reprogramming, an adaptation comprising regulatory processes that countermand injurious effectors and invoke novel neuroprotective pathways. TLRs (Toll-like receptors) play important roles in sensing potential danger/insult in the form of pathogens as well as endogenous stress molecules that occur in response to mild injury (e.g. heat-shock proteins). Recent studies suggest that TLRs are novel and potent preconditioning targets that offer substantial promise to protect the brain from ischaemic injury.