Eclampsia is a serious complication of pregnancy that occurs when hypertension during pregnancy develops with neurologic complications, including headache, vomiting, blindness and convulsions. While multiple organs are affected by hypertension in pregnancy, cerebrovascular involvement is the direct cause of death in ~40% of patients. The major cerebrovascular changes that occur during eclampsia are thought to be similar to hypertensive encephalopathy in which acute elevations in pressure cause autoregulatory breakthrough, hyperperfusion and edema. Our preliminary studies found that late-pregnant animals had significantly decreased cerebrovascular resistance and hyperperfusion compared to nonpregnant animals during acute hypertension, similar to eclampsia. Importantly, only the late-pregnant animals developed cerebral edema, suggesting that pregnancy alone predisposes the brain to the neurologic complications of eclampsia when blood pressure is elevated. Because of the prominent role of edema formation in mediating the neurologic complications of eclampsia, the long-term objective of this project is understand the underlying mechanisms by which pregnancy and hypertension in pregnancy affect the cerebral circulation in a way that promotes hydrostatic brain edema during increased blood pressure. Our preliminary studies suggest for the first time that pregnancy causes outward remodeling of cerebral arterioles, an effect that likely diminishes small vessel resistance in the brain during acute hypertension.
Aim 1 will therefore investigate underlying mechanisms by which pregnancy causes outward remodeling, including the hormone relaxin, known to promote vascular remodeling in the systemic circulation during pregnancy. We also found that pregnancy causes more severe blood-brain barrier disruption in response to acute hypertension compared to nonpregnant animals.
Aim 2 will investigate underlying mechanisms by which this occurs, including production of placental growth factor that can increase hydraulic conductivity and decrease tight junction expression. Lastly, because many women who develop eclampsia have preexisting hypertension, or preeclampsia, prior to the acute hypertensive event that causes neurologic complications, Aim 3 will use a model of hypertension in pregnancy to investigate changes in cerebral hemodynamics, blood-brain barrier properties and edema formation that may be unique compared to normal pregnancy. A powerful combination of in vivo and in vitro techniques will be used that should provide clinically relevant information regarding novel hemodynamic changes and mechanisms of edema during pregnancy and hypertension in pregnancy.

Public Health Relevance

Eclampsia is a leading cause of maternal death world-wide. These studies investigate underlying mechanisms by which pregnancy and hypertension during pregnancy affect the cerebral circulation in ways that promote the neurologic complications of eclampsia. This understanding is crucial to effective management and treatment of this devastating condition.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Hypertension and Microcirculation Study Section (HM)
Program Officer
Bosetti, Francesca
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Vermont & St Agric College
Schools of Medicine
United States
Zip Code
Linfante, Italo; Cipolla, Marilyn J (2016) Improving Reperfusion Therapies in the Era of Mechanical Thrombectomy. Transl Stroke Res 7:294-302
Babi, M Alain; Gorman, Mark J; Cipolla, Marilyn J et al. (2016) Ondansetron-related hemorrhagic posterior reversible encephalopathy syndrome (PRES) following gastric bypass. Springerplus 5:18
Canavero, Isabella; Sherburne, Helene A; Tremble, Sarah M et al. (2016) Effects of Acute Stroke Serum on Non-Ischemic Cerebral and Mesenteric Vascular Function. Transl Stroke Res 7:156-65
Ahnstedt, Hilda; McCullough, Louise D; Cipolla, Marilyn J (2016) The Importance of Considering Sex Differences in Translational Stroke Research. Transl Stroke Res 7:261-73
Johnson, Abbie Chapman; Nagle, Keith J; Tremble, Sarah M et al. (2015) The Contribution of Normal Pregnancy to Eclampsia. PLoS One 10:e0133953
Wallace, Kedra; Tremble, Sarah M; Owens, Michelle Y et al. (2015) Plasma from patients with HELLP syndrome increases blood-brain barrier permeability. Reprod Sci 22:278-84
Hammer, Erica Shields; Cipolla, Marilyn J (2015) Cerebrovascular Dysfunction in Preeclamptic Pregnancies. Curr Hypertens Rep 17:64
Schreurs, M P; Cipolla, M J; Al-Nasiry, S et al. (2015) Formerly eclamptic women have lower nonpregnant blood pressure compared with formerly pre-eclamptic women: a retrospective cohort study. BJOG 122:1403-9
Sweet, Julie G; Chan, Siu-Lung; Cipolla, Marilyn J (2015) Effect of hypertension and carotid occlusion on brain parenchymal arteriole structure and reactivity. J Appl Physiol (1985) 119:817-23
Cipolla, Marilyn J; Sweet, Julie; Chan, Siu-Lung et al. (2014) Increased pressure-induced tone in rat parenchymal arterioles vs. middle cerebral arteries: role of ion channels and calcium sensitivity. J Appl Physiol (1985) 117:53-9

Showing the most recent 10 out of 51 publications