# Spreading Depolarization and Progression of Developmental Epileptic Encephalopathy

> **NIH NS R01** · BAYLOR COLLEGE OF MEDICINE · 2026 · $400,000

## Abstract

PROJECT SUMMARY
Spreading depolarization (SD) is a wave of massive, near-complete cellular depolarization that slowly
propagates across brain tissue. Recent decades of clinical studies have convincingly demonstrated that this
prolonged depolarization wave occurs under certain conditions in the human brain and can contribute to
deleterious acute and chronic neurological deficits. SD is distantly related to seizures, and their co-occurrence
has been observed in numerous clinical and experimental settings. However, the majority of the findings are
based on experimentally evoked SD, often in anesthetized animals. It remains an open question whether SD
spontaneously emerges and contributes to neurological comorbidities in epilepsy patients.
 In order to address the neurological significance of spontaneous SD, we recently developed a chronic DC-band
EEG recording and demonstrated that SD events indeed occur spontaneously in awake genetic and acquired
epilepsy mouse models, each exhibiting distinct generation patterns and interactions with seizures unique to the
respective models. With advanced multimodal electrophysiological and state-of-the-art behavioral analysis tools,
we are now investigating both the neurological consequences and underlying regulatory mechanisms of these
pathophysiological depolarizations in hyperexcitable neuronal circuitries.
 This project will investigate the contributions of SD to epilepsy comorbidities and disease progression in Dravet
syndrome, a major example of developmental epileptic encephalopathy (DEE), using a well-established Scn1a
deficient mouse model (Scn1a+/R1407X). Leveraging our expertise in acute and chronic electrophysiological
monitoring in awake juvenile mice, we will thoroughly characterize the pathological significance of SD events in
the developing juvenile Scn1a+/R1407X mice, in which the risk of premature mortality is high, neurobehavioral
abnormalities begin to emerge, and spontaneous cortical and subcortical SD are prese

## Key facts

- **NIH application ID:** 11361679
- **Project number:** 5R01NS136214-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Isamu  Aiba
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NS
- **Fiscal year:** 2026
- **Award amount:** $400,000
- **Award type:** 5
- **Project period:** 2025-06-26T00:00:00 → 2030-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11361679

## Citation

> US National Institutes of Health, RePORTER application 11361679, Spreading Depolarization and Progression of Developmental Epileptic Encephalopathy (5R01NS136214-02). Retrieved via AI Analytics 2026-05-20 from https://api.ai-analytics.org/grant/nih/11361679. Licensed CC0.

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