Schematic of TLR signaling and gene expression following stroke. (A) TLR4 signaling cascades following stroke. Stroke leads to NF-κB activation without IRF3 activation. (B) LPS (CpG) preconditioning prior to stroke leads to robust activation of IRF3 and type I interferon; meanwhile, the increased Ship1, Tollip, and p105 lead to the suppression of NF-κB activity and pro-inflammation cytokines compared to stroke alone. (C) Pam3CSK4 preconditioning activates the TLR2/PI3K/Akt signaling pathway and subsequently downregulates NF-κB activity and the expression of Bax, as well as increases the expression of Bcl-2, Hsp27, and Hsp70. (D) Poly-IC preconditioning activates IRF3 and induces IFN-β production. (E) GDQ preconditioning activates IRF7 and induces IFN-α production. DAMPs, damage-associated molecular patterns; TLR, toll-like receptor; TRIF, TIR-domain-containing adapter-inducing interferon-β; IRF, interferon regulatory factor; LPS, lipopolysaccharide; Poly-IC, polycytidylic acid; .