Strategies to mitigate muscle mass loss in individuals with spinal cord injury.

Context: Muscle atrophy following spinal cord injury (SCI) is severe, often exceeding rates observed in disuse or critical illness. Neurogenic factors, such as the loss of neural input and disruption of neuromuscular signaling worsen the effects of physical inactivity. The severe muscle loss lowers muscle quality and impairs function, increasing the risk of chronic metabolic diseases. Understanding the mechanisms underlying SCI-induced muscle atrophy is crucial for developing targeted interventions.

Objective: This review examines SCI-induced muscle atrophy mechanisms, addresses limitations of current interventions, and proposes therapeutic strategies integrating exercise mimetics, nutrition, and pharmacological agents to overcome anabolic resistance and improve muscle preservation.

Methods: A PubMed search was conducted using terms including "spinal cord injury", "disuse", "muscle atrophy", "anabolic resistance", "muscle protein metabolism" and "interventions". (Pre)clinical studies and reviews relevant to skeletal muscle physiology after SCI were included.

Results: Anabolic resistance seems to be a key contributor to rapid SCI-induced muscle loss. Motor-complete SCI prevents voluntary contractions, limiting traditional exercise-based interventions. Neuromuscular electrical stimulation (NMES) can mitigate muscle atrophy during immobilization and critical illness especially when combined with protein supplementation. Additional nutritional interventions, including vitamin D, creatine, ursolic acid, polyunsaturated fatty acids (PUFAs), and pharmacological agents such as androgens, myostatin inhibitors, and β2-adrenoceptor agonists, may further attenuate muscle atrophy.

Conclusion: A multidimensional approach integrating NMES, targeted nutrition, and pharmacological strategies may enhance muscle mass retention, metabolic health, and rehabilitation outcomes in individuals with SCI. Further research is needed to refine these interventions and establish clinical guidelines for muscle preservation in this population.