Cerebral Blood Flow Regulation in Pregnancy, Hypertension, and Hypertensive Disorders of Pregnancy

Abstract

The regulation of cerebral blood flow (CBF) allows for the metabolic demands of the brain to be met and for normal brain function including cognition (learning and memory). Regulation of CBF ensures relatively constant blood flow to the brain despite changes in systemic blood pressure, protecting the fragile micro-vessels from damage. CBF regulation is altered in pregnancy and is further altered by hypertension and hypertensive disorders of pregnancy including preeclampsia. The mechanisms contributing to changes in CBF in normal pregnancy, hypertension, and preeclampsia have not been fully elucidated. This review summarizes what is known about changes in CBF regulation during pregnancy, hypertension, and preeclampsia.

Keywords: autoregulation; blood-brain barrier; cerebral blood flow; chronic hypertension; eclampsia; preeclampsia; pregnancy; superimposed preeclampsia.

Figure 1

Cerebral blood flow can be regulated by four major mechanisms: myogenic, neurogenic, metabolic, or endothelial. These mechanisms ensure that cerebral blood flow (CBF) is maintained within a relatively normal range. NO—nitric oxide, ET1—endothelin 1.

Figure 2

Different hypertensive disorders of pregnancy and their relationship to each other. This diagram gives a visual representation of how the varying pregnancy-associated hypertensive disorders overlap. A subset of women can develop eclampsia from any of the hypertensive disorders of pregnancy and can also develop in normotensive patients. The subset of women with chronic hypertension who develop preeclampsia symptoms are diagnosed with superimposed preeclampsia. Some women with gestational hypertension may develop preeclampsia later in the pregnancy. Only chronic hypertension can be diagnosed before the 20th week of gestation.

Figure 3

Dynamic CBF autoregulation differs among the different hypertensive disorders of pregnancy. Compared to normal pregnant women (CTRL), pregnant women with chronic hypertension (CHTN), preeclampsia (PE) or superimposed preeclampsia (SiPE) have significantly lower autoregulatory index during pregnancy while women with gestational hypertension (GHTN) have an autoregulatory index similar to that of the CTRL. Women with superimposed preeclampsia have the lowest autoregulatory index of all hypertensive disorders of pregnancy. * p < 0.05, ** p < 0.01, *** p < 0.001 compared to CTRL. This figure was created using data presented in van Veen, et al. AJOG, 2015 [36].

Figure 4

Summary of cerebrovascular changes associated with hypertension, pregnancy, and preeclampsia. In the hypertensive, non-pregnant state, wall thickness increases and lumen diameter decreases. In pregnancy, there is an adaptive outward remodeling while in preeclampsia, there is a lack of inward remodeling in response to hypertension, causing cerebral blood vessels to be more susceptible to blood brain barrier (BBB) disruption and micro-bleeds. In chronic hypertension, pregnancy reverses the in-ward remodeling of the cerebral vessels. Increased blood pressure and velocities in vessels with thin walls can cause transmittal of pressure to the micro-vessels causing BBB leakage and micro-bleeds. This induces increases in glial cells and chronically, neuroinflammation. Tube-like structures represent capillaries, star-shaped cells represent glia, and red mini-circles represent micro-bleeds.