# Preeclampsia and pre-clinical stages of maternal vascular dementia

> **NIH NIH R01** · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · 2021 · $77,059

## Abstract

Preeclampsia is a hypertensive disorder of pregnancy with consequences extending beyond the perinatal
period for the mother and the offspring. Women a history of preeclampsia are more likely to self-report
cognitive complaints and have impaired attention, learning, and memory, suggesting an association between
pregnancies with preeclampsia and maternal cognitive function. Recent large cohort studies showed that
preeclampsia was associated with increased risk of dementia, particularly vascular dementia, since women
with a history of preeclampsia had more than a 3-fold increased risk of vascular dementia compared with
women with no history of preeclampsia. It is unknown whether dysfunction of the maternal peripheral
vasculature, which is a hallmark of preeclampsia, extends to dysfunction in arteries supplying the brain and
whether preeclampsia causes early signs of neurodegeneration in the maternal brain increasing risk of
maternal cognitive impairment. The proposed studies will investigate the role of placental ischemia (common
feature of pregnancies with preeclampsia) and increased Toll-like receptor-9 activity (TLR-9; documented in
women with preeclampsia) in the development of preclinical stages of maternal dementia. We hypothesize that
placental ischemia induces preclinical stages of maternal dementia through activation of TLR-9 signaling and
this impairment persist postpartum. Aim 1 will determine the effects of a placental ischemia on maternal
cognitive function during pregnancy and postpartum. Hypothesis: Placental ischemia impairs maternal
cognitive function and this impairment persists postpartum. To test this hypothesis, we will measure maternal
hippocampal-dependent cognitive behavior and short-term contextual and episodic memory at the end of
gestation and two months postpartum in an experimental model of preeclampsia with placental ischemia. Aim
2 will determine the contribution of TLR-9 activation to brain neurodegeneration in an experimental model of
preeclampsia with placental ischemia. Hypothesis: Placental ischemia induces maternal brain inflammation
and oxidative stress through activation of TLR-9 signaling. To test this hypothesis, we will measure oxidative
stress and cytokine expression in maternal brain regions implicated in pre-clinical stages of neurodegenerative
diseases in rats with experimental preeclampsia with placental ischemia. Pregnant rats will be treated with
vehicle or a TLR-9 inhibitor. Aim 3 will determine the contribution of TLR-9 activation to vascular impairment in
arteries supplying the maternal brain in an experimental model of preeclampsia with placental ischemia.
Hypothesis: Carotid arteries from rats with experimental preeclampsia have increased stiffness, increased
generation of reactive oxygen species (ROS) and enhanced vasoconstrictor responses and these effects are
mediated by activation of TLR-9 signaling. To test this hypothesis, we will use carotid arteries from rats used
for Aim 2. Successful co...

## Key facts

- **NIH application ID:** 10289448
- **Project number:** 3R01HL146562-02S1
- **Recipient organization:** UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
- **Principal Investigator:** Styliani Goulopoulou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $77,059
- **Award type:** 3
- **Project period:** 2020-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10289448

## Citation

> US National Institutes of Health, RePORTER application 10289448, Preeclampsia and pre-clinical stages of maternal vascular dementia (3R01HL146562-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10289448. Licensed CC0.

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