# Mechanisms of Seizure in Pregnancy and Preeclampsia

> **NIH NIH R56** · UNIVERSITY OF MISSISSIPPI MED CTR · 2021 · $389,514

## Abstract

PROJECT SUMMARY:
Eclampsia, diagnosed in women (pregnant and early postpartum) who experience new onset seizures, can be
deadly to both the mother and fetus. While a large proportion of eclampsia cases affect women with a diagnosis
of preeclampsia, a hypertensive disorder of pregnancy, some women with otherwise healthy pregnancies
develop eclampsia. The mechanisms contributing to seizures during pregnancy are not fully known. Currently,
magnesium sulfate (MgSO4) is administered to preeclampsia patients with severe symptoms and is effective in
preventing seizures when started early. However, the mechanisms by which MgSO4 protects against seizure
activity is not fully known and it is still difficult to predict which women will develop seizures. Our preliminary data
show that in a rat model of preeclampsia, induced by surgical reduction of utero-placental perfusion pressure
(RUPP), seizure sensitivity is increased. We also show that RUPP mice have higher seizure duration and have
decreased acid sensing ion channels (ASIC2a) expression in the hippocampus when compared to pregnant
mice that underwent sham surgery. ASICs are important for maintaining homeostatic pH especially after
increased neuronal activity as occurs in seizures. Genetic knockdown of ASIC2a led to increased seizure
severity and longevity in pregnant mice indicating that ASIC2a is important for seizure termination. In this
application, we propose to test the hypothesis that MgSO4 acts by reducing inflammation (IL-17 levels) which
allows ASICs to function normally to restore homeostatic tissue pH. We will focus on the role of ASIC2a in
mediating increased seizure activity in our mouse RUPP model of preeclampsia. We will utilize mice with genetic
knockdown of ASIC2a and IL-17ra (the IL-17 receptor) and induce seizures pharmacologically using
pentylenetetrazol. We will use acute administration of MgSO4 to assess the mechanisms of action in preventing
or reducing seizure activity in mice subjected to sham or RUPP surgery. We propose to answer the following
questions: 1) Does knockdown of ASIC2a exacerbate RUPP-induced increases in seizure sensitivity? 2) Is
ASIC2a required for MgSO4 to have anti-seizure effects in our mouse model of preeclampsia? 3) Is increased
IL-17 responsible for RUPP-induced increases in seizure sensitivity and does IL-17 regulate ASIC2a expression?
By answering these questions, we will identify new therapeutic targets for eclampsia and will have a better
understanding of the mechanisms of action of MgSO4 which represents major advances in the field of neurology
and obstetrics.

## Key facts

- **NIH application ID:** 10279955
- **Project number:** 1R56HL159447-01
- **Recipient organization:** UNIVERSITY OF MISSISSIPPI MED CTR
- **Principal Investigator:** Junie Paula Warrington
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $389,514
- **Award type:** 1
- **Project period:** 2021-09-20 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10279955

## Citation

> US National Institutes of Health, RePORTER application 10279955, Mechanisms of Seizure in Pregnancy and Preeclampsia (1R56HL159447-01). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10279955. Licensed CC0.

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