Section ? Wallace, Kedra Hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome affects 10-20% of women with severe preeclampsia. Studies have identified HELLP syndrome as a condition of pregnancy in which women are affected with hypertension, neurological compromise, immune system dysregulation, and dysregulation of the soluble placental factors, sFlt-1 and sEndoglin, which are significantly increased compared to women with preeclampsia and with normal pregnancies. Circulating CD{4}+ T cells and inflammatory cytokines, both of which are significantly increased in women with HELLP syndrome and to a lesser extent in women with gestational hypertension, can increase blood brain barrier (BBB) permeability and lead to neuroinflammation. Based on several studies reporting changes in mood and cognition after HELLP syndrome and the preliminary data presented in this proposal, the central hypothesis to be tested is that the increase in circulating CD{4}+ T cells that occurs in pregnancies with hypertension and inflammation contributes to BBB permeability and neuroinflammation during pregnancy. Additionally, children born to women with HELLP syndrome and some women who experience a hypertensive pregnancy have developmental delays and altered cognitive function, which could be due to the compromised in utero environment. We will also test the hypothesis that the increase in maternal CD{4}+ T cells contributes to growth restricted and developmentally delayed offspring.
Specific Aim 1. To test the hypothesis that during pregnancy hypertension and inflammation mediated by CD{4}+ T cells contribute to BBB disruption in an animal model of HELLP syndrome and in an animal model of gestational hypertension we will adoptively transfer CD{4}+T cells during pregnancy to determine their effects on BBB integrity and on the development of neuroinflammation.
Specific Aim 2. To examine the effect of hypertension and increased T cells during pregnancy on rat pup neurodevelopment, immune profile and hypertensive susceptibility we will assess neurodevelopment, sensorimotor skills and inflammation in pups subjected to immune system blockade or hypertension during pregnancy.
Section ? Kedra Wallace Some women with hypertensive and/or immune sensitive pregnancies (preeclampsia and HELLP syndrome) have evidence of increased blood brain barrier permeability and neuroinflammation. Babies born to women with these conditions are also at risk for neurodevelopment and sensorimotor delays. The studies outlined in this project will determine the role of CD{4}+ T cells in contributing to the hypertension and neuroinflammation in animals with HELLP syndrome or animals with gestational hypertension. We will also examine the role of immune suppression on rat pup neurodevelopment and hypertensive susceptibility.
