# Pathological SUR1-TRPM4 Expression in Neurons Heightens Chronic Seizure Susceptibility

> **NIH NIH F31** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $38,306

## Abstract

Project Summary/Abstract
Current anti-seizure medications are insufficient for managing seizures in epilepsy patients, as they become less
effective over time and are associated with significant side effects. One promising molecular target for reducing
seizures is the SUR1-TRPM4 channel. This channel is a sodium conducting ion channel not significantly
expressed in healthy brain that upregulates de novo in neurons in other seizure-related disease pathologies such
as stroke and traumatic brain injury. SUR1-TRPM4 upregulation is a disease-specific pathologic mechanism that
has been successfully targeted and shown to be effective in reducing stroke pathology through preclinical studies
and clinical trials. Preliminary data demonstrate that SUR1-TRPM4 expression increases in neurons in epileptic
tissues resected from patients and in a pentylenetetrazol (PTZ) kindling rodent model of epilepsy. Furthermore,
pharmacological inhibition of SUR1-TRPM4 in vitro prevents neuronal population hyperactivity induced by low
Mg2+, and inhibiting SUR1-TRPM4 in vivo using pharmacologic inhibitors (glyburide, 9-phenanthrol) or genetic
knock-out (KO) globally or specifically in neurons attenuates the development of seizures induced by PTZ
kindling. This proposal aims to define the contributions of neuronal SUR1-TRPM4 expression to chronic seizure
activity by assessing the effects of neuron-specific SUR1-TRPM4 overexpression on neuronal hyperexcitability
in vitro and seizure susceptibility in vivo. This proposal fits the NINDS mission of reducing neurologic disease
burden, has rapid translatable potential due to the SUR1 inhibitor glyburide being FDA approved, and could
improve current anti-seizure medications by identifying a new epilepsy-specific therapeutic target not significantly
expressed in healthy brain tissue. This research will be conducted across two labs with specific expertise in the
SUR1-TRPM4 channel and epilepsy at a state-of-the-art institution in the University of Maryland School of
Medicine. I will gain valuable experience in molecular and electrophysiologic techniques, particularly for inducing
protein overexpression and data collection and analysis of neuronal firing via calcium imaging and
electroencephalogram (EEG). Toward that end, this project will continue my development towards my ultimate
career goal of becoming an independently funded neurosurgeon-scientist focused on translational and clinical
research in epilepsy.

## Key facts

- **NIH application ID:** 10994835
- **Project number:** 1F31NS135752-01A1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Mitchell Bradley Moyer
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $38,306
- **Award type:** 1
- **Project period:** 2024-08-01 → 2025-04-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10994835

## Citation

> US National Institutes of Health, RePORTER application 10994835, Pathological SUR1-TRPM4 Expression in Neurons Heightens Chronic Seizure Susceptibility (1F31NS135752-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10994835. Licensed CC0.

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