Role of Toll-like receptor mediated signaling in traumatic brain injury.

The mechanisms underlying secondary brain damage following traumatic brain injury (TBI) remain unclear. A great many studies have demonstrated that inflammatory cascades contribute to brain damage through the activation of immune/inflammatory responses, including the increased release of cytokines and chemokines, and the recruitment of leukocytes. The cells and tissues damaged by primary mechanical injury release a number of endogenous factors acting as damage-associated molecular patterns (DAMPs), which initiate and perpetuate noninfectious inflammatory responses through transduction signaling pathways. Toll-like receptors (TLRs) are a transmembrane receptor family that can recognize the specific DAMPs released from damaged cells and recruit a set of adaptors leading to the activation of downstream kinases and nuclear factors which regulate the expression of inflammatory genes. The activation of inflammatory responses mediated by TLR signaling is closely associated with brain tissue damage and neurological dysfunction following TBI. TLRs and their downstream protein kinases may be potential targets for the treatment of TBI. Modulation of TLR-mediated signaling may attenuate brain damage and improve TBI outcome. In this review, we briefly discuss the role of TLR-mediated signaling in TBI and the new treatments targeting TLR signaling. This article is part of the Special Issue entitled "Novel Treatments for Traumatic Brain Injury".