# Hippocampal arteriole remodeling and brain injury in preeclampsia and eclampsia

> **NIH NIH R01** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2020 · $390,000

## Abstract

Preeclampsia (PE) is a common hypertensive disorder of pregnancy that causes significant maternal and fetal
morbidity and mortality worldwide. The consequences of PE extend far beyond pregnancy and are associated
with excessive cardiovascular and cerebrovascular disease risk later in life, including a 9-fold increased risk of
dying from myocardial infarction and a 4- to 5-fold increased risk of stroke. PE women also have high seizure
susceptibility (called eclampsia) that causes considerable morbidity and mortality both during seizure and later
in life. Importantly, former PE and eclamptic women (seizure in a PE woman) have poorer cognition and brain
atrophy later in life, with increased white matter lesions on magnetic resonance imaging (MRI) that positively
correlate with cognitive defects and decline. The effect of PE and eclampsia on memory and cognition
suggests the hippocampus is adversely affected, a brain region that has a critical role in consolidation of long-
and short-term memory and spatial navigation. Our previous studies found that hippocampal arterioles (HAs),
small brain arterioles that perfuse the hippocampus, were smaller and stiffer in a model of experimental PE
(ePE) than HAs from normal late-pregnant animals that was associated with mild cognitive impairment. In
addition, ePE animals lacked a hyperemic response to seizure that was associated with greater neuronal
injury. Thus, the overall goal of this proposal is to investigate vascular mechanisms of hippocampal injury and
cognitive impairment during PE and eclampsia. The overall hypothesis of this application is that HA remodeling
and increased stiffness during ePE causes hippocampal injury that promotes cognitive impairment. We will
therefore investigate mechanisms by which HA remodeling and increased stiffness occurs in ePE and if
preventing the vascular changes will prevent cognitive impairment (Aim 1). We will also determine the effect of
prolonged and recurrent seizure on hippocampal injury and if preventing HA remodeling will prevent injury
during seizure (Aim 2). And lastly, we will determine if the vascular and cognitive changes persist long-term
(months postpartum) in ePE rats (Aim 3). The proposed studies will provide a greater understanding of the
mechanisms by which cognitive impairment occurs in women with PE and how seizure adversely affects the
maternal brain. The potential outcome of this project is identifying new therapeutic targets and strategies for
preventing and/or treating hippocampal injury in women with PE and eclampsia that could improve the lives of
women with this condition.

## Key facts

- **NIH application ID:** 9919008
- **Project number:** 5R01NS108455-03
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** Marilyn J Cipolla
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9919008

## Citation

> US National Institutes of Health, RePORTER application 9919008, Hippocampal arteriole remodeling and brain injury in preeclampsia and eclampsia (5R01NS108455-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9919008. Licensed CC0.

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