Schematic of TLR4 signaling and gene expression following stroke. (Top) TLR4 signaling cascades following stroke. In the absence of LPS preconditioning, stroke leads to NFκB activation without IRF3 activation. LPS preconditioning prior to stroke leads to robust activation of IRF3 and suppressed NFκB activity compared to stroke alone. (Bottom) Gene expression 24 hr post stroke. Stroke alone dramatically upregulates pro-inflammatory genes. LPS preconditioning prior to stroke dramatically upregulates anti-inflammatory/Type I IFN genes, many of which are associated with IRF3, while still maintaining a pro-inflammatory response.