Using the Reduced Uterine Perfusion Pressure model of preeclampsia to study the blood brain barrier permeability

Daniele Cristóvão Escouto, Giovani Gadonski, Luiz Porcello-Marrone, Jaderson Costa da Costa, Nathália Paludo, Rayssa Ruszkowski do Amaral, Bartira Ercília Pinheiro da Costa, Carlos Eduardo Poli-de-Figueiredo


AIMS: To use the Reduced Uterine Perfusion Pressure (RUPP) model for preeclampsia to describe and evaluate the blood brain barrier permeability in pregnant rats.

METHODS: Forty-one pregnant Wistar rats were divided into different intervention groups between 13 to 15 days of gestation: Pregnant-Control (PC; n=12), Reduced Uterine Perfusion Pressure (RUPP; n=15), Invasive Blood Pressure-Control (IBP; n=7) and Reduced Uterine Perfusion Pressure and Invasive Blood Pressure (RUPP-IBP; n=7). The 14 rats of groups IBP and RUPP-IBP had their mean arterial pressure measured at day 21. All animals were then sacrificed, administered Evans Blue dye through the tail vein and perfused with paraformaldehyde 4%. Brains were removed and evaluated by a blinded pathologist. Results are presented as means and standard errors. Comparisons between the groups were performed using Student's t-test for continuous variables and Fisher’s exact test for categorical variables. Statistical significance was set as a p value less than 0.05.

RESULTS: Mean arterial pressure averaged 85.4±2.2 mmHg in the IPB group and 102.5±8.3 mmHg in the RUPP-IPB group (p=0.002). Among all the RUPP rats (RUPP and RUPP-IBP groups), 82% had a positive staining with Evans Blue dye for at least one of the brain hemispheres, while none of the pregnant control rats (PC and IBP groups) had brain staining (p<0.001).

CONCLUSIONS: In this study, altered permeability of the blood brain barrier was successfully reproduced in pregnant rats exposed to the RUPP protocol. Therefore, we concluded that the RUPP model is a valid surrogate to study blood brain barrier abnormalities.


animal models; blood-brain barrier; preeclampsia; eclampsia; toxemia of pregnancy; hypertension; posterior leukoencephalopathy syndrome; pregnancy complications.

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