Pediatrics & Women's Health
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/32089
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Browsing Pediatrics & Women's Health by Author "Cromartie, Whitney"
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Item Changes in cerebral inflammation and blood pressure in postpartum preeclamptic rats(2023) Wiemann, Natalia; Smith, Jonna; Smith, Savanna; Jones, Kylie; Castillo, Angie; Cromartie, Whitney; Owen, Malissa; McCafferty, Adair; Srivastava, Prakriti; Cunningham, MarkIntroduction: Postpartum (PP) preeclamptic (PE) women have an increased risk of developing hypertension (HTN) and cerebrovascular diseases later in life. Studies show that women who experience preeclampsia go on to develop HTN 7-8 years earlier than women with normal pregnancies, increasing their risk for developing cerebrovascular diseases such as stroke. While the timing and mechanisms contributing to a rise in blood pressure (BP) and cerebrovascular dysfunction in postpartum preeclamptic women are unknown, they are hypothesized to be influenced by inflammation. Previous studies in our lab indicate postpartum PE rats at 10 weeks have HTN and increased inflammation (PMID: 34727994). Our current study will examine BP and inflammation in postpartum PE rats at an earlier time point, 6 weeks (PP6), to determine the relationship between cerebral inflammation and the pathophysiology of HTN. We hypothesize that postpartum PE rats will have an increase in BP and cerebral inflammation 6 weeks after delivery. Methods: Pregnant Sprague Dawley rats were divided into 2 groups: normal pregnant (NP) rats, and preeclamptic (RUPP) rats. Placental ischemia was surgically induced in the preeclamptic group via the reduced uterine perfusion pressure (RUPP) model. All rats gave birth naturally and were weaned for 3 weeks. At PP6, BP was measured via carotid catheterization, and brain tissue was collected to measure pro-inflammatory (TNF-α and IL-17) and anti-inflammatory (IL-4 and IL-10) factors via colorimetric assays and ELISAs. Results: Blood pressure was elevated in RUPP PP vs NP PP (128±6 vs 106±4mmHg, p<0.05). Cerebral TNF-α drastically increased by ~2.4 fold in RUPP PP vs NP PP (2576±445.6 vs 1058±212.5pg/mL, ns). Cerebral IL-17(331.2±41.1 vs 297.6±48.6pg/mL, ns) and IL-4 (178.4±23.4 vs 154.8±14pg/mL, ns) also increased in RUPP PP vs NP PP. Cerebral IL-10 (103.9±21.4 vs 147.6±11.3pg/mL, ns) was decreased in RUPP PP vs NP PP rats. Conclusion: PP6 preeclamptic rats have HTN and increased cerebral inflammation. It is yet to be determined whether cerebral inflammatory markers are the cause or consequence of HTN in PP6 PE rats. Future studies will explore the sequence of HTN and cerebral inflammation in postpartum PE rats and determine how brain inflammation contributes to HTN and cerebral damage. We will also target specific areas of the brain that modulate autonomic function and BP. This study is clinically relevant because it will inform providers on the pathophysiology of HTN and/or cerebral damage in women after a PE pregnancy. Our findings suggest that the use of inflammatory therapeutic targets improves HTN and cerebrovascular dysfunction in postpartum PE women.Item A new rodent model of preeclampsia: Pregnant daughters from hypertensive placental ischemic moms have hypertension(2023) Smith, Jonna; Powell, Madison; Cromartie, Whitney; Smith, Savanna; Jones, Kylie; Castillo, Angie; Wiemann, Natalia; McCafferty, Adair; Owen, Malissa; Srivastava, Prakriti; Cunningham, MarkPurpose: Studies show that daughters from hypertensive pregnancies are twice as likely to have preeclampsia (PE), pregnancy-induced hypertension (HTN) in comparison to women born from a normal pregnancy. PE affects ~5-10% of all births in the USA and is the leading cause of intrauterine growth restriction (IUGR). PE is associated with oxidative stress (OS) and cerebral damage. The causes of PE are unknown but is influenced by genetic and environmental conditions. Studies show that pregnancies involving placental insufficiency and HTN create an adverse environment that can affect the IUGR baby’s developmental programming and pregnancy outcomes. This study aims to characterize the pregnancy of IUGR rat offspring from hypertensive placental ischemic moms. We hypothesize female rats born from pregnant hypertensive placental ischemic moms will have elevated blood pressure (BP) and OS. Methods: Pregnant Sprague Dawley moms are divided into 2 groups: normal pregnant (NP) and the reduced uterine perfusion pressure (RUPP) hypertensive placental ischemic rats. On day 14 of pregnancy, the RUPP surgery is performed to generate PE. All dams (NP and RUPP) give birth naturally and weaned for 3 weeks. Offspring were then separated by sex and mother’s pregnancy status. ~10 weeks later, offspring were mated according to 4 groups: ♀NP x ♂NP (CON Preg, n=3), ♀NP x ♂RUPP (n=2), ♀RUPP x ♂NP (IUGR Preg, n=5), ♀RUPP x ♂RUPP (n=4). On day 19 of offspring pregnancy, BP was measured via carotid catheterization and the blood and brains were collected for analyses. Results: IUGR Preg rats have elevated BP (116 ± 4.17 vs 100.6 ± 2.54 mmHg, p<0.02) and 8-isoprostanes (439.2 ± 13.61 vs 381.3 ± 26.10 g, ns), decreased circulating antioxidant capacity (AC) (0.33 ± 0.01 vs. 0.37 ± 0.01 mM Trolox/mg protein, p<0.01), and reduced body weight (330.1 ± 5.24 vs 350.3 ± 10.82 g, ns) compared to CON Preg rats. IUGR Preg rats have larger brains, suggesting brain swelling (5.38 ± 0.10 vs 4.95 ± 0.19 g/1000g BW, p<0.04). HSP-1 (186.1 ± 28.14 vs 100.0 ± 6.36 %HSP-1/protein/CON, p<0.04) and H2O2 (25.76 ± 2.95 vs 15.81 ± 4.56 μM/mg protein, ns), markers of ROS, are increased in the brains of IUGR Preg vs. CON Preg rats. Cerebral AC was slightly reduced (260.0 ± 33.14 vs 292.3 ± 13.91 uM Trolox/mg protein) and MnSOD (antioxidant) amounts were decreased (87.96 ± 3.43 vs 100.0 ± 2.84 %MnSOD/protein/CON, p<0.63). Conclusion: IUGR Preg rats have increased systemic and cerebral OS, as well as larger brain sizes which may lead to cerebral damage. In summary, pregnant daughters from hypertensive placental ischemic moms show symptoms of a preeclamptic-like phenotype, thus creating a new model of PE. Future studies will determine the role of maternal PE status and OS in the development of HTN in pregnant IUGR offspring.