Abstract 016: Placental Ischemia Exposure leads to a Pro-Inflammatory Environment in Brains of Embryonic Day 19 Rat Offspring

Abstract

Placental ischemia is thought to be the initiating event in the pathophysiology of preeclampsia, a hypertensive disorder of pregnancy. Previous studies have shown that placental ischemia in the rat, induced by surgically reducing uterine perfusion pressure (RUPP), leads to increased circulating pro-inflammatory cytokines and anti-angiogenic factors, similar to the preeclampsia patient. It is not known whether pups exposed to placental ischemia have evidence of neuroinflammation in utero ; therefore, this study assessed whether placental ischemia contributes to a pro-inflammatory environment in brains of offspring at embryonic day (E)19. Sham or RUPP surgery was performed on timed-pregnant Sprague Dawley rats (260g) on gestational day 14, and pup brains were extracted on E19. Using a multi-plex cytokine/chemokine kit, we found that 7 out of 27 cytokine/ chemokines were significantly increased in brain homogenates from pups exposed to placental ischemia (n=5 pup brains/group). Higher levels of Eotaxin (5.76±0.26 vs. 3.86±0.84 pg/mg protein; p=0.03), Interleukin (IL)-1β (5.17±0.25 vs. 3.70±0.43 pg/mg; p=0.01), IL-6 (72±10.5 vs. 46.3±7.01 pg/mg; p=0.04), LIX (CXCL5; 45.8±2.2 vs. 30.4±4.7; p=0.01), IL-17 (1.12±0.51 vs. 0.27±0.03; p=0.02), IL-18 (330.1±40.9 vs. 226.5±18.3; p=0.02), and macrophage inflammatory protein 2 (MIP-2; 20.8±0.5 vs. 15.7±1.9 pg/mg; p=0.02) were observed in pup brains exposed to placental ischemia. Despite these increases in pro-inflammatory cytokines, brain water content, measured in a different group of pups from same dams, was not different between the two groups (87.77±0.05 vs. 87.73±0.35%, p=0.53). Whether the increase in pro-inflammatory cytokines in brains of rat pups exposed to placental ischemia is a result of increased transport across the placental barrier or a compensatory mechanism to the hypoxic environment is not known. Our findings support the hypothesis that neuroinflammation in the offspring exposed to placental ischemia may contribute to neurodevelopmental disorders and cognitive impairment observed in offspring of preeclampsia-complicated pregnancies.