Model of toll-like receptor (TLR) preconditioning-induced protection. Strokes cause the release of damage-associated molecular patterns (DAMPs). Once released, the DAMPs bind and activate TLRs. Non-preconditioned TLRs respond to DAMPs by activating an inflammatory response that increases ischemic damage. In preconditioned TLR the response to the presence of DAMPs has been reprogrammed by previous exposure to a TLR ligand. Consequently, they activate an interferon regulatory factor (IRF)-mediated response that is associated with neuroprotection. HMGB1, high mobility group box 1; HSPs, heat shock proteins; Prx, peroxiredoxin protein.