# Neurovascular Unit Dysfunction in Women with Severe Preeclampsia

> **NIH NIH K23** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $192,183

## Abstract

PROJECT SUMMARY/ABSTRACT
 The overall goal of this career development proposal is for me to learn, develop and use translational
approaches to investigate postpartum neurovascular dysfunction in women with preeclampsia. To achieve this,
I will work with a multidisciplinary team of mentors and collaborators including both clinical and basic scientists.
 Preeclampsia (PEC), a multisystem disorder occurring in 3-8% of pregnancies,1,2 is characterized by
hypertension during the second half of pregnancy and widespread endothelial dysfunction. PEC increases the
risk of maternal stroke up to 6-fold,1,3 and strokes account for 40-70% of maternal deaths in women with
PEC.4,5 Most strokes occur in the first 2 weeks postpartum, often after women have been discharged home.6,7
PEC shares features with the reversible cerebral vasoconstriction syndrome and the posterior reversible
encephalopathy syndrome.8,9 These three conditions often overlap in women with postpartum stroke, and are
leading causes of ischemic stroke, subarachnoid hemorrhage and intracerebral hemorrhage in this population.
We have no biomarkers to predict which women with PEC will develop these devastating complications.
 The mechanisms by which PEC leads to postpartum stroke are poorly understood. The neurovascular
unit, comprising endothelial cells, smooth muscle cells, pericytes, astrocytes, neurons, and extracellular matrix
proteins, maintains the structural integrity of the blood-brain barrier. The neurovascular unit also mediates
cerebral autoregulation, or the ability of the cerebral vasculature to regulate cerebral blood flow in response to
rapid changes in blood pressure. Human and animal studies have implicated abnormalities in both
autoregulatory and blood-brain barrier properties of the neurovascular unit in PEC-related cerebrovascular
dysfunction.10-15 Animal studies have suggested faulty vascular endothelial growth factor (VEGF) signaling and
inflammation may lead to PEC-associated neurovascular unit dysfunction.10,12,16
 My central hypothesis is that the neurovascular unit is compromised in peripartum women with severe
PEC, due to inflammation and disruptions in VEGF signaling causing both cerebral autoregulatory dysfunction
and blood-brain barrier compromise. In the 5-year period of grant support, I will conduct a prospective study in
a cohort of 80 pregnant women with and without severe PEC. In Aim 1, I will use transcranial Doppler and non-
invasive blood pressure monitoring to test postpartum cerebral autoregulatory function, correlating the results
with levels of VEGF-related proteins and inflammatory cytokines in serum and cerebrospinal fluid collected
from study participants at the time of delivery. In Aim 2, I will expose cultured human brain endothelial cells to
the same biospecimens to determine the role of VEGF signaling pathways in PEC-associated blood-brain
barrier dysfunction. Through these complementary but independent aims, I hope to identify physiological and
se...

## Key facts

- **NIH application ID:** 9929645
- **Project number:** 5K23NS107645-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Eliza C Miller
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $192,183
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9929645

## Citation

> US National Institutes of Health, RePORTER application 9929645, Neurovascular Unit Dysfunction in Women with Severe Preeclampsia (5K23NS107645-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9929645. Licensed CC0.

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