Dose-dependent lipopolysaccharide-induced fetal brain injury in the guinea pig

OBJECTIVE: This study determined whether a lipopolysaccharide (LPS) dose-dependent increase in fetal brain injury occurs to further characterize the relationship between maternal inflammation and fetal brain injury. STUDY DESIGN: Pregnant guinea pigs (n = 59) at 70% gestation were injected intraperitoneally with 1, 5, 25, 50, 100, 200, or 300 mu g LPS per kilogram of maternal body weight or an equivalent volume of vehicle. Animals were killed 7 days later. Maternal serum and amniotic fluid samples were assayed for proinflammatory cytokines tumor necrosis factor-alpha, interleukin- 1 beta, and interleukin- 6 using enzyme- linked immunosorbent assay kits. Fetal brains (n = 72) were stained for evidence of cell death with NeuroTACS stain. RESULTS: Seven days after LPS injections, cytokine concentrations in maternal serum and amniotic fluid were not different (P > .05) from controls. Levels of cell death in all brain regions examined were highest following the maternal administration of 300 mu g/ kg LPS (P < .05). The dose effect was brain region-dependent (P <.05). CONCLUSION: A threshold of maternal infection/ inflammation exists, beyond which demonstrable fetal brain injury may result.