Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)




Eclampsia is a hypertensive disorder of pregnancy and a leading cause of maternal death. The primary explanation for eclampsia is that it represents a form of hypertensive encephalopathy (HTE) with neurological symptoms including headaches, nausea, vomiting, visual disturbances, and seizures. The etiology of HTE involves an acute increase in arterial blood pressure that exceeds the autoregulatory capacity of the brain leading to forced dilatation of cerebral vessels, decreased cerebrovascular resistance, hyperperfusion, blood-brain barrier (BBB) disruption, and vasogenic cerebral edema formation. Due to the central role of the cerebral circulation in mediating these symptoms, a better understanding of how pregnancy affects the cerebral circulation is important to the treatment and prevention of eclampsia. A central goal of this dissertation was to determine pregnancy’s effect on cerebral blood flow (CBF) autoregulation, edema formation, and BBB permeability during acute hypertension. Women with eclampsia often seize at lower blood pressures than HTE patients. We hypothesized that pregnancy may predispose the brain to eclampsia by lowering the pressure of autoregulatory breakthrough and enhancing cerebral edema formation. Using an in vivo model of HTE, we found that the pressure of autoregulatory breakthrough was not different between nonpregnant (NP) and late-pregnant (LP) rats; however, cerebral edema formation was significantly increased only in LP animals. Nitric oxide synthase inhibition significantly increased the upper limit of autoregulation in both NP and LP animals and attenuated cerebral edema formation in LP animals. BBB permeability during acute hypertension was not different between these groups. Magnesium sulfate (MgSO4) is widely used to treat eclampsia despite an unclear mechanism of action. A second goal of this dissertation was to determine the cerebrovascular effects of MgSO4 during pregnancy. Specifically, we investigated the effect of MgSO4 on in vitro resistance artery vasodilation and in vivo BBB permeability during acute hypertension. We hypothesized that dilation to MgSO4 would be greater in mesenteric than cerebral vessels. MgSO4 elicited concentration-dependent vasodilation in all arteries, as determined by measuring lumen diameter of isolated and pressurized arteries, however, mesenteric arteries were considerably more sensitive than cerebral arteries. In addition, there was no effect of pregnancy on MgSO4 sensitivity in mesenteric arteries, whereas pregnancy decreased sensitivity to MgSO4 in cerebral arteries. We further hypothesized that MgSO4 would decrease BBB disruption during acute hypertension, thereby protecting the brain in eclampsia. Using an in vivo model of HTE, we showed that MgSO4 treatment decreased BBB permeability during acute hypertension in LP rats, with the greatest effect observed in the posterior cerebrum. In conclusion, this dissertation determined CBF autoregulation and cerebral edema formation during pregnancy, and also the effect of MgSO4 on cerebral resistance artery vasodilation and BBB permeability during acute hypertension in LP rats. Although pregnancy did not influence autoregulatory breakthrough, cerebral edema formation was enhanced in LP animals and this may potentiate neurological symptoms in eclampsia. In addition, MgSO4-induced cerebral vasodilation is likely not a primary mechanism of eclampsia treatment, rather MgSO4 may limit edema formation by attenuating BBB permeability during hypertension.