# Stroke Outcome in Pregnancy and Preeclampsia

> **NIH NIH R21** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2021 · $429,000

## Abstract

PROJECT SUMMARY
Stroke in pregnancy is a major health problem in the US, with an incidence that is 3-fold higher than stroke rates
in comparable nonpregnant women. Pregnancy-related stroke has a profound and devastating impact on a
women’s life and her ability to care for her child or children. Complicating the public health concerns even more
is the fact pregnancy-related strokes in the United States is on the rise. The increased risk of stroke in pregnancy
is largely driven by the comorbidity of preeclampsia (PE), a hypertensive disorder that complicates up to 10% of
all pregnancies. In fact, greater than 1/3 of women with pregnancy-related stroke have comorbid PE, increasing
the risk of stroke 6-fold vs. women without PE. Relevant to this proposal, stroke in pregnancy is largely unstudied.
Pregnant women have been excluded from randomized stroke clinical trials and therefore nothing is known about
treatment and outcome in this population. This R21 proposal is to provide critically needed information on stroke
injury and outcome in pregnancy and PE. Our overall hypothesis is that the maternal brain is more susceptible
to ischemia and reperfusion injury than age-matched nonpregnant females and that this susceptibility is further
exacerbated by PE. This hypothesis is based on our published and preliminary data demonstrating increased
neuronal excitability and brain injury in a rat model of normal pregnancy that is further increased in a model of
PE. In addition, PE is a state of high oxidative stress and neuroinflammation that could exacerbate stroke injury.
Remarkably, it is unknown how pregnancy and PE affect stroke outcome. Aim 1 will use a model of transient
focal ischemia in nonpregnant, normal pregnant and PE rats to determine stroke outcome (infarct, cellular injury,
neurologic deficit and mortality) as well as contributors to injury, including perfusion deficit, collateral flow and
reperfusion injury (edema and hemorrhagic transformation). Aim 2 will acutely treat with clinically relevant doses
of magnesium sulfate (MgSO4), a safe and effective treatment in pregnancy that has been used for decades to
prevent brain hyperexcitability and seizure. MgSO4 is a calcium antagonist that prevents glutamate-induced
excitotoxic injury and may be beneficial in preventing stroke injury in pregnancy and PE, an excitotoxic state.
Importantly, we will use MgSO4 in combination with tissue plasminogen activator (tPA) since tPA has been shown
to interfere with stroke treatment. tPA alone will also be studied since it is standard of care yet the safety and
therapeutic window is not known in pregnancy or PE. It is our hope that the results of this project will lead to
better treatment of stroke in pregnancy.

## Key facts

- **NIH application ID:** 10228815
- **Project number:** 1R21NS120419-01A1
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** Marilyn J Cipolla
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $429,000
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10228815

## Citation

> US National Institutes of Health, RePORTER application 10228815, Stroke Outcome in Pregnancy and Preeclampsia (1R21NS120419-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10228815. Licensed CC0.

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