TLR-4-dependent and -independent mechanisms of fetal brain injury in the setting of preterm birth

In this study, we sought to assess how essential activation of toll-like receptor 4 (TLR-4) is to fetal brain injury from intrauterine inflammation. Both wild-type and TLR-4 mutant fetal central nervous system cells were exposed to inflammation using lipopolysaccharide in vivo or in vitro. Inflammation could not induce neuronal injury in the absence of glial cells, in either wild-type or TLR-4 mutant neurons. However, injured neurons could induce injury in other neurons regardless of TLR-4 competency. Our results indicate that initiation of neuronal injury is a TLR-4-dependent event, while propagation is a TLR-4-independent event.