# Sequence of physiological events during oxygen conserving reflex activation leading to sudden death in epilepsy

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $79,577

## Abstract

Project Summary
Recent SUDEP research points to serotonin as a key neurotransmitter involved in apnea and death, but most
research into serotonin signaling pathways focuses on serotonin signaling in the central nervous system. Our
animal experiments modeling SUDEP have shown that the carotid body, a peripheral structure, plays a major
role in the progression of fatal apnea. I will explore how peripheral intervention through the carotid body
impacts respiration by observing how serotonin and serotonergic compounds affect oxygen conserving
reflexes during acute seizure experiments (Aim 1) and using photopharmacology (light-mediated drug delivery)
to localize pharmaceutical interventions to the carotid body (Aim 2) in acute seizure experiments with oxygen
conserving reflexes.
Aim 1 will probe serotonin mechanisms in ictal respiratory crisis from our animal model that we can compare to
mechanisms observed in clinical seizure cases. This may further validate the animal SUDEP model and could
also imply an effective way to stratify SUDEP risk for patients.
Aim 1 will help answer whether promoting serotonin signaling can prevent respiratory failure leading to sudden
death. Administering serotonin intracranially and systemically will help explore how seizure affects serotonin
signaling pathways and determine whether systemic upregulation of serotonin can mitigate these effects.
Similarly, administering serotonergic compounds will provide insight into how pharmaceutical treatments
prescribed for other serotonin disorders impact respiration during seizure.
Aim 2 will explore how targeted serotonin administration affects respiratory pathways implicated in SUDEP.
Photocaged serotonin will enable me to only administer serotonin to a region illuminated with the proper
wavelength of light. This will clarify the role of the carotid body in respiratory signaling and, if photorelease of
serotonin succeeds in preventing sudden death, this could lead to the development of a chronic device to
prevent SUDEP in at-risk patients.
In addition to yielding useful, fundamental mechanistic data about how serotonin impacts respiratory crisis,
both inside and outside seizure, the techniques used to generate this data also bear clinical translation
relevance. The experimental methods developed here may reasonably transition to practical clinical diagnostic
and therapeutic strategies.

## Key facts

- **NIH application ID:** 10622708
- **Project number:** 3R01NS119390-03S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Pedro Irazoqui
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $79,577
- **Award type:** 3
- **Project period:** 2020-12-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10622708

## Citation

> US National Institutes of Health, RePORTER application 10622708, Sequence of physiological events during oxygen conserving reflex activation leading to sudden death in epilepsy (3R01NS119390-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10622708. Licensed CC0.

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