Chorioamnionitis induced by intraamniotic lipopolysaccharide resulted in an interval-dependent increase in central nervous system injury in the fetal sheep.

Abstract

We quantified the impact of chorioamnionitis on both the white and gray matter structures of the preterm ovine central nervous system (CNS). The CNS was studied at 125 days of gestation, either 2 or 14 days after the intraamniotic administration of 10 mg of lipopolysaccharide (LPS) (Escherichia coli) or saline. Apoptotic cells and cell types were analyzed in the brain, cerebellum, and spinal cord using flow cytometry. Apoptosis and microglial activation increased in all regions with prolonged exposure to LPS-induced chorioamnionitis. Astrocytes were increased in the brain and cerebellum of LPS-exposed fetuses but not in the spinal cord. Mature oligodendrocytes decreased in the cerebral and cerebellar white matter, the cerebral cortex, caudate putamen, and hippocampus 14 days after LPS. Neurons in the cerebral cortex, hippocampus, and substantia nigra were reduced 14 days after LPS. Fetal inflammation globally but differentially affected the CNS depending on the maturational stage of the brain region.