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.
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.
|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|
|Merhi, Zaher; Doswell, Angela; Krebs, Kendall et al. (2014) Vitamin D alters genes involved in follicular development and steroidogenesis in human cumulus granulosa cells. J Clin Endocrinol Metab 99:E1137-45|
|Cipolla, Marilyn J; Chan, Siu-Lung; Sweet, Julie et al. (2014) Postischemic reperfusion causes smooth muscle calcium sensitization and vasoconstriction of parenchymal arterioles. Stroke 45:2425-30|
|Schreurs, Malou P H; Cipolla, Marilyn J (2014) Cerebrovascular dysfunction and blood-brain barrier permeability induced by oxidized LDL are prevented by apocynin and magnesium sulfate in female rats. J Cardiovasc Pharmacol 63:33-9|
|Palomares, Sara M; Cipolla, Marilyn J (2014) Myogenic tone as a therapeutic target for ischemic stroke. Curr Vasc Pharmacol 12:788-800|
|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|
|van der Wijk, Anne-Eva; Schreurs, Malou P H; Cipolla, Marilyn J (2013) Pregnancy causes diminished myogenic tone and outward hypotrophic remodeling of the cerebral vein of Galen. J Cereb Blood Flow Metab 33:542-9|
|Schreurs, Malou P H; Cipolla, Marilyn J (2013) Pregnancy enhances the effects of hypercholesterolemia on posterior cerebral arteries. Reprod Sci 20:391-9|
|Chan, Siu-Lung; Sweet, Julie G; Cipolla, Marilyn J (2013) Treatment for cerebral small vessel disease: effect of relaxin on the function and structure of cerebral parenchymal arterioles during hypertension. FASEB J 27:3917-27|
|Chapman, Abbie C; Cipolla, Marilyn J; Chan, Siu-Lung (2013) Effect of pregnancy and nitric oxide on the myogenic vasodilation of posterior cerebral arteries and the lower limit of cerebral blood flow autoregulation. Reprod Sci 20:1046-54|
Showing the most recent 10 out of 37 publications