Eclampsia is a serious complication of pregnancy that occurs when hypertension develops with neurologic symptoms, including headaches, nausea, visual disturbances and convulsions. While numerous organs are affected by hypertension in pregnancy, cerebrovascular involvement is the direct cause of death in approximately 40 percent of patients. The major cerebrovascular changes that occur have been shown to be similar to hypertensive encephalopathy in which acute elevations in blood pressure (i.e., acute hypertension) overcome the myogenic vasoconstriction of the cerebral arteries and arterioles causing autoregulatory failure, hyperperfusion and edema. Because women who develop eclampsia in general are normotensive prior to pregnancy, there is evidence that pregnancy affects the cerebral circulation in a way that makes the vessels susceptible to autoregulatory failure and hyperperfusion during acute hypertension. The long-term objective of this proposal is to investigate how pregnancy affects the structure and function of the cerebral circulation focusing on diameter regulation in response to changes in pressure (myogenic reactivity) and how those changes affect vascular permeability that promotes edema.
Aim 1 will use isolated and pressurized posterior cerebral arteries from pregnant and nonpregnant rats to determine the pressure at which forced dilatation occurs and investigate underlying mechanisms of pregnancy-induced alterations in diameter regulation, including vascular smooth muscle actin and endothelial cell influences (e.g., nitric oxide and prostaglandins). In addition, since hypertension alone has been shown to cause significant remodeling and reactivity changes in the cerebral circulation, Aim 1 will also investigate how elevated mean arterial pressure during pregnancy affects myogenic activity and diameter regulation in a rat model of hypertension in pregnancy (nitric oxide inhibition). Acute hypertension and eclampsia are associated with significant edema formation due to disruption of the normally impermeable cerebral endothelium. Therefore, Aim 2 will investigate pregnancy-induced changes in endothelial cell permeability during acute hypertension, including enhanced fluid phase endocytosis (transcellular flux) and tight junction disruption (paracellular flux). The influence of pregnancy on permeability during forced dilatation will be determined using a combination of techniques, including clearance of fluorescent tracers and transmission electron microscopy. ? ?

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Cardiovascular and Renal Study Section (CVB)
Program Officer
Golanov, Eugene V
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
Johnson, Abbie C; Cipolla, Marilyn J (2018) Impaired function of cerebral parenchymal arterioles in experimental preeclampsia. Microvasc Res 119:64-72
Johnson, Abbie C; Hammer, Erica S; Sakkaki, Sophie et al. (2018) Inhibition of blood-brain barrier efflux transporters promotes seizure in pregnant rats: Role of circulating factors. Brain Behav Immun 67:13-23
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
Linfante, Italo; Cipolla, Marilyn J (2016) Improving Reperfusion Therapies in the Era of Mechanical Thrombectomy. Transl Stroke Res 7:294-302
Ahnstedt, Hilda; Sweet, Julie; Cruden, Patrick et al. (2016) Effects of Early Post-Ischemic Reperfusion and tPA on Cerebrovascular Function and Nitrosative Stress in Female Rats. Transl Stroke Res 7:228-38
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
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
Johnson, Abbie C; Cipolla, Marilyn J (2016) Altered hippocampal arteriole structure and function in a rat model of preeclampsia: Potential role in impaired seizure-induced hyperemia. J Cereb Blood Flow Metab :271678X16676287
Merhi, Zaher; Thornton, Kimberley; Bonney, Elizabeth et al. (2016) Ovarian kisspeptin expression is related to age and to monocyte chemoattractant protein-1. J Assist Reprod Genet 33:535-43
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

Showing the most recent 10 out of 56 publications