Uteroplacental inflammation results in blood brain barrier breakdown, increased activated caspase 3 and lipid peroxidation in the late gestation ovine fetal cerebellum

Maternal infection is associated with perinatal brain damage, but effects on the cerebellum are not known in detail. In this study, we examined the effects of placental inflammation induced by administering lipopolysaccharide into the uterine artery of pregnant sheep at 134-136 days gestation. The fetal brain was collected 72 h later and compared to brains collected from age-matched untreated fetuses. Placental lipopolysaccharide treatment had substantial effects on the fetal cerebellum, including increasing the number of cells undergoing apoptosis, widespread lipid peroxidation, and extravasation of plasma albumin, suggesting compromise of the cerebellar blood-brain barrier. These effects may account for some of the learning and motor deficits that emerge in neonates from pregnancies compromised by infection.