TLR ligand transport across the blood-brain barrier. (A) Circulating LPS binds to endothelial cells in the brain vasculature and transmits inflammatory signals to the brain via COX-2- and NF-κB-associated pathways. Alternatively, LPS in the circulation induces release of cytokines from circulating blood cells, which can either affect the integrity of the blood-brain barrier (B) or be transported across the intact blood-brain barrier (C) to induce further inflammation in the brain parenchyma.