Treatments to restore respiratory function after spinal cord injury and their implications for regeneration, plasticity and adaptation

Exp Neurol, 2012 · DOI: 10.1016/j.expneurol.2011.12.018 · Published: May 1, 2012

Spinal Cord Injury Pulmonology Neuroplasticity

Simple Explanation

Spinal cord injuries, especially in the neck area, can severely impact breathing because they disrupt the nerve signals that control the diaphragm. This review explores different methods to restore breathing after such injuries, focusing on how the nervous system's ability to adapt and change (plasticity) can be harnessed to improve respiratory function. One approach involves using drugs like theophylline to stimulate the respiratory system and activate dormant pathways that can compensate for the damaged ones. Another method involves intermittent hypoxia, which is exposing the body to short periods of low oxygen, which can trigger long-lasting improvements in respiratory motor output. Researchers are also investigating ways to promote the regrowth of damaged nerve fibers and modify the spinal cord's respiratory neurons to enhance their function. These strategies aim to tap into the spinal cord's inherent capacity to reorganize and adapt in response to injury, ultimately leading to improved breathing and quality of life for SCI patients.

Study Duration

Not specified

Participants

Animal models (rats, cats, dogs) and preliminary evidence from two SCI incomplete patients

Evidence Level

Not specified

Key Findings

1
Pharmacological treatments, such as theophylline, can partially restore function to the paralyzed hemidiaphragm by increasing respiratory drive.
2
Intermittent hypoxia (IH) protocols, both acute (AIH) and chronic (CIH), can elicit long-lasting increases in respiratory motor output, a phenomenon known as long-term facilitation (LTF).
3
Chondroitinase ABC (ChABC) treatment, which degrades inhibitory molecules in the glial scar, can promote regeneration of axons back into the CNS from peripheral nerve grafts, leading to functional improvements.

Research Summary

This review highlights experimental strategies to restore respiratory function after spinal cord injury (SCI), focusing on the innate plasticity and capacity for adaptation in the respiratory system and its associated circuitry in the spinal cord. Various methods, including pharmacological treatments, intermittent hypoxia, and promoting axonal regeneration, have shown promise in restoring respiratory function after SCI. A multi-faceted strategy that combines several approaches may be necessary to fully restore respiratory function and improve outcomes for the SCI community.

Practical Implications

Pharmacological Interventions

Theophylline and other respiratory stimulants can be used to activate latent respiratory pathways and improve breathing after SCI.

Intermittent Hypoxia Therapy

AIH and CIH protocols can be explored as potential therapies to enhance respiratory motor output and promote functional recovery after SCI.

Regenerative Strategies

Combining peripheral nerve grafts with ChABC treatment can promote axonal regeneration and improve respiratory function by overcoming inhibitory factors in the glial scar.

Study Limitations

1
The C2 hemisection model, while useful, cannot be advanced to a full transection to affect all respiratory-related muscles.
2
Diaphragm function alone may not be sufficient to sustain life and quality of life in SCI patients with impaired inspiratory capacity.
3
The rat model has limitations in translating findings to human patients, particularly regarding the importance of accessory respiratory muscles.

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