Activity-Based Physical Rehabilitation with Adjuvant Testosterone to Promote Neuromuscular Recovery after Spinal Cord Injury

International Journal of Molecular Sciences, 2018 · DOI: 10.3390/ijms19061701 · Published: June 7, 2018

Spinal Cord Injury Endocrinology Rehabilitation

Simple Explanation

Spinal cord injuries (SCI) often lead to impaired neuromuscular function and reduced musculoskeletal health, hindering recovery. Activity-based therapies (ABTs) aim to promote neuromuscular plasticity but are limited by SCI severity. Many men with SCI also experience low testosterone, potentially worsening these impairments. Adding testosterone to ABTs may enhance musculoskeletal recovery and neuroplasticity. Testosterone can help prevent muscle loss and promote motoneuron survival after SCI. While testosterone alone may not provide significant functional improvements, combining it with ABTs like bodyweight-supported treadmill training (BWSTT) could lead to more comprehensive recovery. This review explores the molecular reasons for muscle loss after SCI, the separate effects of testosterone and locomotor training, how these strategies work, and the potential of combining ABT with testosterone for better recovery.

Study Duration

Not specified

Participants

Humans and rodent models

Evidence Level

Review

Key Findings

1
Low testosterone levels are common after SCI and may exacerbate muscle loss and neuromuscular impairment.
2
Activity-based therapies (ABTs) promote neuromuscular plasticity after SCI, but their effectiveness decreases with increasing SCI severity.
3
Combining testosterone with ABTs, such as BWSTT, may lead to more comprehensive neuromusculoskeletal recovery than either strategy alone, based on preliminary data.

Research Summary

SCI leads to muscle loss and impaired mitochondrial function, partly due to increased FOXO signaling and reduced PGC-1α/β expression. Testosterone promotes muscle anabolism and anticatabolic effects, potentially enhancing activity-mediated neuromuscular plasticity after SCI. Preliminary data suggests that combining testosterone with BWSTT results in greater musculoskeletal and neuromuscular improvement and recovery of voluntary plantar stepping after moderate-severe contusion SCI.

Practical Implications

Combined Therapy Potential

Combining testosterone therapy with activity-based rehabilitation may offer enhanced recovery outcomes for individuals with SCI.

Targeted Molecular Mechanisms

Understanding the molecular mechanisms underlying the benefits of testosterone and ABTs can lead to more targeted therapeutic interventions.

Personalized Treatment

Assessing testosterone levels in men with SCI and tailoring treatment plans to address hormonal deficiencies may improve rehabilitation outcomes.

Study Limitations

1
Lack of published randomized studies evaluating testosterone as an adjuvant to BWSTT.
2
Potential side effects of TRT, such as polycythemia and prostate-related events, require careful evaluation.
3
Further research is needed to elucidate the molecular mechanisms underlying the combined benefits of testosterone and ABTs.

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