# Promoting and understanding recovery of breathing after chronic spinal cord injury

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2020 · $337,094

## Abstract

PROJECT SUMMARY/ABSTRACT
 More than 50% of all spinal cord injuries occur at the cervical level. At this level are the phrenic motor
neurons which innervate the diaphragm. Therefore, injuries at this level can lead to the inability to breathe.
The overall objective of this grant proposal is to examine the changes which take place chronically in the
phrenic circuitry of the cord in response to cervical spinal cord injury and investigate and optimize potential
therapies that can restore breathing long after injury. Through these studies, an effective intervention can be
translated to a significant population of the spinal cord injured community. In this proposal we will utilize
chronic cervical spinal cord-hemisected animals which have half of the diaphragm paralyzed. In our earlier
studies we observed that enzymatic (chondroitinase ABC) removal of extracellular matrix molecules, called
chondroitin sulfate proteoglycans, which block plasticity, regeneration, and sprouting, led to restoration of
function of the once paralyzed hemidiaphragm when administered at or near the time of injury. Recovered
diaphragmatic activity was rhythmic and synchronized. In stark contrast, when the spinal cord of chronically
injured animals was stimulated with chondroitinase ABC and intermittent hypoxia training, chaotic and
unstructured activity resulted, suggesting slowly developing and potentially maladaptive responses to injury.
However, the use of chondroitinase alone at chronic stages can promote normal rhythm and dramatically
enhance properly patterned functional recovery. This grant proposal seeks to: 1) understand the time course
and carefully describe the maladaptive processes that take place; 2) understand the mechanisms underlying
the production of this newly discovered atypical activity at chronic time points; and 3) learn how to overcome
these negative responses to injury so that interventions and rehabilitative strategies can become more
effective, thereby leading to improved functional outcomes. Overall, these studies will provide insight on the
basic mechanisms that underlie maladaptive, as well as functionally beneficial plasticity that can lead to robust
functional respiratory motor recovery at chronic stages of spinal cord injury.

## Key facts

- **NIH application ID:** 9872210
- **Project number:** 5R01NS101105-04
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Warren Joseph Alilain
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $337,094
- **Award type:** 5
- **Project period:** 2017-03-15 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872210

## Citation

> US National Institutes of Health, RePORTER application 9872210, Promoting and understanding recovery of breathing after chronic spinal cord injury (5R01NS101105-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9872210. Licensed CC0.

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