Cerebral Edema and Blood Brain Barrier Dysfunction in the Dahl S Rat Model of Superimposed Preeclampsia

• Published in: The FASEB journal Vol. 31; no. S1
• Main Authors: Maeda, Kenji John, Warrington, Junie P, Duncan, Jeremy, Granger, Joey P, Garrett, Michael R, Ryan, Michael J, Sasser, Jennifer M
• Format: Journal Article
• Language: English
• Published: 01-04-2017
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.31.1_supplement.lb857

Abstract only Preeclampsia, characterized by hypertension and renal dysfunction in pregnancy, is associated with placental ischemia, which has been linked to increased blood‐brain barrier permeability and cerebral edema. We recently demonstrated that pregnant Dahl salt sensitive rats (Dahl S) closely mimic the maternal syndrome of preeclampsia. In this study, we tested the hypothesis that pregnant Dahl S rats develop cerebral vascular dysfunction associated with encephalopathies commonly observed in preeclamptic women. To test this, pregnant Dahl S and Sprague Dawley (SD, healthy pregnancy control) rats were studied during late pregnancy (gestational day 20, n=4–6). Mean arterial pressure (MAP) was significantly greater on day 20 of pregnancy in the Dahl S rat compared to SD (153±11 vs. 107±3 mmHg, p<0.05), and there was no drop in MAP during pregnancy in the Dahl S compared to virgin littermates (141±12, p=0.48). To assess blood‐brain barrier function, Evan's Blue extravasation into the brain was measured. Evan's Blue concentration was increased in both posterior (0.04±0.012 vs. 0.018±0.001 ng/g tissue/plasma concentration, p=0.07) and anterior (0.021±0.001 vs. 0.034±0.006, p=0.06) brain in pregnant Dahl S rats compared to virgin littermates, respectively. No difference was observed in either brain region in SD rats. In a separate group of Dahl S pregnant and virgin rats (n=5), brains were harvested and weighed on day 20, heated at 50°C for 72 hours, and weighed again to determine the dry:wet weight ratio as a measure of brain water content (edema). Greater water content was found in the posterior brain of the pregnant Dahl S compared to virgin littermates (78.0±0.1 vs. 77.4±0.2, p<0.05) with no significant difference in the anterior brain (79.2±0.2 vs. 78.8±0.3, p=0.33). These results suggest that the Dahl S rat model of superimposed preeclampsia exhibits blood brain barrier dysfunction and cerebral edema. Therefore, pregnant Dahl S rats may be a useful model to investigate mechanisms leading to cerebral vascular abnormalities that occur during preeclampsia.
Support or Funding Information
National Institutes of Health, American Society of Nephrology, UMMCIRSP