Pharmacologic approaches to prevent skeletal muscle atrophy after spinal cord injury

Curr Opin Pharmacol, 2021 · DOI: 10.1016/j.coph.2021.07.023 · Published: October 1, 2021

Spinal Cord Injury Pharmacology Musculoskeletal Medicine

Simple Explanation

Spinal cord injury (SCI) leads to rapid muscle wasting due to nerve damage and paralysis. This muscle loss is made worse by inflammation, low testosterone and IGF-1 levels, and steroid treatments. The signals causing muscle loss after SCI are similar to those in other types of disuse, but SCI causes faster atrophy. Anabolic agents like androgens don't work as well, but ursolic acid and β2-agonists can help. Combining physical therapy to reload the paralyzed limbs with drugs that target the molecular pathways involved in muscle loss holds the greatest promise for improving muscle recovery after severe SCI.

Study Duration

Not specified

Participants

Persons with spinal cord injury and animal models

Evidence Level

Review article

Key Findings

1
Muscle loss after SCI is more rapid than in other disuse conditions, with distinct molecular signaling cascades.
2
Anabolic agents, including androgens, display diminished ability to prevent SCI-induced atrophy.
3
Ursolic acid and β2-agonists more effectively attenuate muscle loss.

Research Summary

Severe SCI leads to rapid muscle atrophy due to neural insult, paralysis, systemic inflammation, hormonal imbalances, and glucocorticoid treatment. The review discusses the SCI muscle phenotype, molecular signaling pathways, secondary factors influencing muscle atrophy, and recent pharmacologic approaches to lessen muscle loss. Combining physical rehabilitation with drugs targeting underlying molecular pathways offers the greatest potential for muscle recovery after severe SCI.

Practical Implications

Targeted Therapies

Develop pharmacologic agents targeting specific signaling pathways in atrophic muscle after SCI.

Combination Approaches

Combine drugs that suppress atrophy and stimulate anabolic pathways with activity-based physical therapies.

Early Intervention

Administer interventions early after SCI to prevent rapid muscle loss.

Study Limitations

1
Limited effectiveness of anabolic agents in SCI-induced atrophy.
2
Difficulty in simultaneously suppressing atrophy and stimulating anabolic pathways.
3
Need for elucidating the complexity of signaling pathways driving SCI-induced muscle loss.

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