Synergy Between Acute Intermittent Hypoxia and Task-Specific Training

Exerc Sport Sci Rev, 2020 · DOI: 10.1249/JES.0000000000000222 · Published: July 1, 2020

Spinal Cord Injury Neuroplasticity Neurorehabilitation

Simple Explanation

Acute intermittent hypoxia (AIH) and task-specific training (TST) synergistically improve motor function after spinal cord injury. The mechanisms underlying this synergistic relationship are unknown, but a hypothetical working model involving neural networks and cellular elements is proposed to explain it. The model suggests that AIH primes the nervous system by broadly increasing BDNF (brain-derived neurotrophic factor) synthesis. TST then further elevates BDNF in specific neural circuits activated during the practiced motor task, leading to enhanced plasticity and motor recovery. This combined effect results in a greater improvement in motor function than what would be expected from either treatment alone. The review emphasizes the need for future research to test and refine this model, with the goal of optimizing AIH-TST therapy for neurological disorders.

Study Duration

Not specified

Participants

Rats and humans with spinal cord injury

Evidence Level

Review, Model development

Key Findings

1
Combined AIH and TST produce a synergistic effect on motor plasticity, resulting in greater functional benefits than either treatment alone.
2
AIH broadly elevates BDNF synthesis in diverse neural circuits, priming the system for plasticity.
3
TST further elevates BDNF above a functional threshold for motor plasticity only in neural circuits activated during the specific motor task practiced.

Research Summary

After spinal trauma, motor functions are impaired, and new strategies are needed to fully restore function. Acute intermittent hypoxia is a novel intervention with promise to improve respiratory and non-respiratory motor function after SCI by promoting plasticity through targeted increases in BDNF/TrkB signaling. The AIH-TST synergy is specific to the engaged motor function, and does not appear to be generalizable to off-target motor functions.

Practical Implications

Optimization of AIH-TST Therapy

Understanding the mechanisms of AIH-TST synergy may enable optimization of AIH-TST therapy for SCI and other neuromuscular disorders.

Development of New Treatments

Insights from the model could lead to the development of new treatments for neuromuscular disorders that compromise movement, such as amyotrophic lateral sclerosis, Pompe disease, and multiple sclerosis.

Conceptual Translation to Other Neuromodulation Forms

The model's principles could be conceptually translated to other forms of neuromodulation and/or plasticity, such as closed-loop vagal nerve, epidural, or transcutaneous spinal cord stimulation.

Study Limitations

1
The model is highly speculative and requires extensive testing to validate its assumptions.
2
There is currently no empirical evidence supporting the notion that TST elevates BDNF within specific, activated vs. non-activated motor neurons.
3
The possibility remains that synergy may result instead in the motor cortex, or other regions affected both by AIH and TST.

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