Pharmacologic approaches to prevent skeletal muscle atrophy after spinal cord injury

Skeletal muscle atrophy is a hallmark of severe spinal cord injury (SCI) that is precipitated by the neural insult and paralysis. Additionally, other factors may influence muscle loss, including systemic inflammation, low testosterone, low insulin-like growth factor (IGF)-1, and high-dose glucocorticoid treatment. The signaling cascades that drive SCI-induced muscle loss are common among most forms of disuse atrophy and include ubiquitinproteasome signaling and others. However, differing magnitudes and patterns of atrophic signals exist after SCI versus other disuse conditions and are accompanied by endogenous inhibition of IGF1/PI3K/Akt signaling, which combine to produce exceedingly rapid atrophy. Several well-established anabolic agents, including androgens and myostatin inhibitors, display diminished ability to prevent SCI-induced atrophy, while ursolic acid and b2-agonists more effectively attenuate muscle loss. Strategies combining physical rehabilitation regimens to reload the paralyzed limbs with drugs targeting the underlying molecular pathways hold the greatest potential to improve muscle recovery after severe SCI.

Automated summary

Muscle atrophy is a common result of severe spinal cord injury, driven by signaling cascades such as ubiquitinproteasome signaling. Strategies combining physical rehabilitation regimens with drug targeting molecular pathways hold the greatest potential to improve muscle recovery after SCI.