# CSRD Research Career Scientist Award Application

> **NIH VA IK6** · JOHN D DINGELL VA MEDICAL CENTER · 2021 · —

## Abstract

The prevalence of obstructive sleep apnea (OSA) is higher in Veterans compared to the general
populace and the occurrence is increased further in Veterans with spinal cord injury. Thus, OSA
is a major health concern in the Veteran population. Adjustments in the neural modulation of the
arousal threshold (AT), chemoreflex sensitivity to hypoxia and hypercapnia (CS) and upper
airway patency are three critical factors that contribute to exacerbation of sleep apnea. The
exact neuromodulators that control these variables are enigmatic, but one possibility is
serotonin (5HT) and its target receptors. Thus, plasticity of 5HT neurons may account for
modifications in the AT, CS, upper airway patency and ultimately breathing stability in intact and
spinal cord injured (SCI) animals. We are exploring the role of 5HT in modulating those factors
that exacerbate sleep apnea in intact and SCI mice.
If not treated promptly, OSA may result in autonomic, cardiovascular, neurocognitive and
metabolic abnormalities. Treatment of OSA in many cases does not lead to significant
improvements in outcome measures. This inadequacy may be a consequence of reduced
treatment compliance with continuous positive airway pressure (CPAP) and/or because factors
other than those directly linked to sleep apnea contribute to the presence of coincident co-
morbidities. Consequently, innovative therapies that increase CPAP compliance and/or directly
impact those co-morbidities typically associated with OSA independent of CPAP treatment
could improve outcomes linked to sleep apnea. My laboratory has established that mild
intermittent hypoxia (MIH) initiates sustained increases in chest wall and upper airway muscle
activity in humans. This sustained increase is a form of respiratory plasticity known as long-term
facilitation (LTF). Repeated daily exposure to MIH that leads to the initiation of LTF of upper
airway muscle activity could lead to increased stability of the upper airway. In line with my
laboratory's mandate to develop innovative therapies to treat sleep apnea, this increased
stability could ultimately reduce the CPAP required to treat OSA. This reduction, coupled with
our published findings which showed that exposure to MIH increases the arousal threshold,
could lead to improved compliance with CPAP. Improved compliance could ultimately serve to
mitigate those co-morbidities linked to sleep apnea. Moreover, in addition to improving CPAP
compliance, numerous studies indicate that MIH has many direct beneficial cardiovascular,
neurocognitive and metabolic effects. Thus, we are presently exploring if MIH can be used to
both directly and indirectly (via improved CPAP compliance) target and mitigate those co-
morbidities linked to sleep apnea.

## Key facts

- **NIH application ID:** 10100333
- **Project number:** 1IK6CX002287-01
- **Recipient organization:** JOHN D DINGELL VA MEDICAL CENTER
- **Principal Investigator:** Jason H. Mateika
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-10-01 → 2025-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10100333

## Citation

> US National Institutes of Health, RePORTER application 10100333, CSRD Research Career Scientist Award Application (1IK6CX002287-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10100333. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*