# Hyperbaric oxygen therapy mitigates respiratoryneuromuscular pathology after spinal cord injury

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2021 · $381,250

## Abstract

ABSTRACT
Hyperbaric oxygen (HBO) therapy involves brief (≤1 hr) exposure to pressurized oxygen at ≤3 ATM and is used
frequently for wound healing and decompression sickness. Our preliminary data and literature reports have led
to the central hypothesis that HBO, delivered in the acute phases (days to weeks) after cervical spinal cord injury
(SCI), attenuates diaphragm atrophy and dysfunction, reduces cervical spinal cord pathology, and improves
respiratory neuromuscular recovery. The proposed mechanistic link between HBO therapy and attenuation of
both muscular and neural pathology after SCI is oxidative stress. Preliminary data demonstrate that cervical
contusion injury leads to substantial increases in ROS in the diaphragm and atrophy. Preliminary testing also
showed that 1 hr HBO therapy for 10 days decreased diaphragm ROS formation and increased diaphragm
antioxidant capacity. The HBO therapy also considerably attenuated the atrophy and contractile impairments
that occurred after cervical contusion. In regards to spinal neuropathology, secondary damage (i.e., pathology
that develops after the initial trauma) impairs motor recovery. Preliminary histological and molecular data
demonstrate a neuroprotective impact of HBO with reduction in secondary damage in the contused cervical
spinal cord. This includes attenuated neuronal loss with reduced expression of apoptotic markers and reduced
inflammation after HBO therapy. Since oxidative stress contributes to secondary damage, we predict that HBO-
induced upregulation of antioxidant expression underlies these effects. Collectively, the preserved diaphragm
function and attenuated cervical pathology lead to our overall hypothesis that respiratory recovery will be
improved by HBO therapy. Aim 1 will test the hypothesis that HBO therapy during acute through sub-acute
phases after cervical SCI reduces diaphragm atrophy and improves contractility. The hypothesis will be tested
with histological, molecular and functional evaluation of the diaphragm. To test oxidative mechanisms, antisense
oligonucleotides will be used to block translation of specific antioxidants during HBO therapy. To determine if
antioxidant mechanisms are sufficient to explain the HBO therapeutic effects, we will overexpress specific
antioxidants using adeno-associated virus (AAV). Aim 2 will test the hypothesis that the neuroprotective impact
of HBO therapy during acute through sub-acute phases after cervical SCI leads to improved phrenic motor
recovery. The hypothesis will be tested with histological, molecular, and neurophysiological methods (direct
phrenic nerve recordings and diaphragm electromyography). As in Aim 1, mechanistic studies will utilize
antisense oligonucleotides and AAV strategies to modulate antioxidant formation in the spinal cord. Co-PI Dr.
Smuder is an expert in diaphragm biology and mechanisms of atrophy. Co-PI Dr. Fuller has extensive experience
in preclinical SCI models of respiratory dysfunction. Consultant Dr...

## Key facts

- **NIH application ID:** 10232153
- **Project number:** 5R01HL153140-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** DAVID D FULLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $381,250
- **Award type:** 5
- **Project period:** 2020-08-09 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10232153

## Citation

> US National Institutes of Health, RePORTER application 10232153, Hyperbaric oxygen therapy mitigates respiratoryneuromuscular pathology after spinal cord injury (5R01HL153140-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10232153. Licensed CC0.

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