Pharmacological disinhibition enhances paced breathing following complete spinal cord injury in rats

Respir Physiol Neurobiol, 2020 · DOI: 10.1016/j.resp.2020.103514 · Published: November 1, 2020

Simple Explanation

Respiratory problems are a major issue after spinal cord injury, often requiring mechanical ventilators. This study explores an alternative approach using epidural stimulation (EDS) combined with drugs that reduce inhibition in the spinal cord to improve breathing. The researchers tested whether blocking GABA and glycine receptors, which are involved in spinal inhibition, could enhance the effects of EDS on breathing after a complete spinal cord injury in rats. The study found that combining EDS with these drugs significantly improved phrenic motor output, tidal volume, and diaphragm activity, suggesting that spinal inhibition limits breathing capacity after spinal cord injury.

Study Duration

Not specified

Participants

21 adult Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
Combining high-frequency epidural stimulation (HF-EDS) with GABA and glycine receptor antagonists (GABAzine and strychnine) significantly increased phrenic motor output compared to HF-EDS alone.
2
The combination of HF-EDS with GABAzine and strychnine resulted in significantly increased tidal volume compared to HF-EDS alone.
3
The combination of HF-EDS with GABAzine and strychnine resulted in significantly increased amplitude of diaphragm electrical activity compared to HF-EDS alone.

Research Summary

This study investigated whether combining high-frequency epidural stimulation (HF-EDS) with pharmacological disinhibition of spinal circuits could improve breathing after complete high cervical spinal cord injury (SCI) in rats. The researchers found that intrathecal delivery of GABA and glycine receptor antagonists (GABAzine and strychnine) in combination with HF-EDS at the C4 spinal segment significantly increased phrenic motor output, tidal volume, and diaphragm electrical activity compared to HF-EDS alone. The findings suggest that spinal fast inhibitory mechanisms limit phrenic motor output after cervical SCI and represent a potential neuropharmacological target to improve paced breathing in individuals with cervical SCI.

Practical Implications

Improved Respiratory Support

The combination of HF-EDS and pharmacological disinhibition could offer an alternative or adjunct to mechanical ventilation for individuals with cervical SCI.

Targeted Neuropharmacological Intervention

The study identifies spinal fast inhibitory mechanisms as a potential target for improving paced breathing in individuals with cervical SCI, paving the way for targeted neuropharmacological interventions.

Optimization of EDS

The findings suggest that optimizing HF-EDS with intrathecal delivery of GABAz + STR could enhance diaphragm pacing via EDS, potentially replacing conventional artificial ventilation.

Study Limitations

1
Experiments were performed in decerebrate, unanesthetized rats, which may not fully represent the complexity of respiratory control in humans.
2
The study focused on acute effects (6 hours post-C1 transection), and long-term effects of the combined treatment were not evaluated.
3
The study used a complete C1 transection model, which may not fully reflect the variability of human spinal cord injuries.

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