Lipopolysaccharide-Induced Chorioamnionitis Causes Acute Inflammatory Changes in the Ovine Central Nervous System

Objective: To better understand the inflammatory response in the central nervous system (CNS) after lipopolysaccharide (LPS)-induced chorioamnionitis. Study Design: Fetal sheep were exposed to intra-amniotic LPS 2 or 14 days before preterm delivery at 125 days of gestation. mRNA levels of cytokines, TLRs and anti-oxidants were determined in different CNS regions. Results: Interleukin 1 beta levels increased in hippocampus, cortex and cerebellum 2 days after LPS exposure, while Interleukin 8 levels increased in the periventricular white matter as well. Levels returned back to control levels after 14 days. Tumor necrosis factor-alpha levels increased in hippocampus and cortex after 2 days. Toll like receptor 4 levels was upregulated in all grey matter regions 2 and 14 days after exposure. Glutathione s-transferase mRNA levels were lower after 2 and 14 days in all grey matter regions. Conclusion: Intra-amniotic LPS exposure causes acute and region-specific changes in inflammatory markers in the fetal brain, with grey matter being more affected than white matter. Condensation: Intra-amniotic LPS exposure causes acute and region-specific changes in cytokines, TLR and anti-oxidants levels, with grey matter being more affected than white matter.