Clenbuterol, a beta2-adrenoceptor agonist, reduces scoliosis due to partial transection of rat spinal cord

Abstract

Injury to the spinal cord often results in abnormal lateral curvature of the spine, or scoliosis, that is associated with neuromuscular weakness. The lateral curvature of the spine is thought to be a consequence of insufficient or asymmetrical loading of the vertebrae. To study neuromuscular scoliosis, an animal model of spinal cord injury was used in which the spinal cord was partially (3/4) transected, with the left lateral columns left intact. Partial transection of the spinal cord in the rat caused scoliosis that was maximal four to five vertebrae distal to the lesion site. As in previous experiments involving unilateral spinal cord lesions, the scoliotic curves were convex on the weakened side. Subtotal transection at T5 or T11 resulted in lateral displacement of vertebrae T9-T12 or L2-L5, respectively, of up to 11 mm. Interestingly, this vertebral displacement is greatly reduced by clenbuterol, a beta2-adrenoceptor agonist that has been found to retard loss of muscle contractility and bone mineralization due to denervation. Together these results suggest that stimulation of beta2-receptors opposes vertebral unloading due to neuromuscular weakness and thereby acts as a countermeasure to scoliosis.

Role of β-Adrenoceptor Signaling in Skeletal Muscle: Implications for Muscle Wasting and Disease

“…␤-Agonist administration has been proposed as a strategy to attenuate the loss of muscle mass (and function) following denervation (6,7,19,137,213,241,279,281,480,483) or muscle unloading (4,110,376,450,476), with application to the muscle atrophy associated with plaster casting, joint pinning, or extended periods of weightlessness, such as during space flight.…”

Effects of Co-Administration of Clenbuterol and Testosterone Propionate on Skeletal Muscle in Paraplegic Mice

“…Results from various animal models showed that clenbuterol can prevent muscle mass loss, although it remains unclear what its actions are at the single cell level in individual fibers (Zeman et al, 1997(Zeman et al, , 1999. Also, some tests have been conducted with testosterone in SCI patients, but mainly to study spermatogenesis, muscle strength, and locomotor recovery (Clark et al, 2008;Gregory et al, 2003;Huang et al, 1999).…”

Clenbuterol reduces degeneration of exercised or aged dystrophic (mdx) muscle

“…1,8,12,16,19,36,40,41 Consistent with increased muscle strength and loading, skeletal abnormalities including demineralization and scoliosis that result from neuromuscular weakness are also improved by ␤ 2 -agonist treatment. 38,39 The ability of ␤ 2 -agonists to reduce muscle atrophy and to stimulate hypertrophy may account for improved strength 36,37 in some neuromuscular diseases. On the other hand, the effects of ␤ 2 -agonists on muscle fiber necrosis and loss, a primary cause of weakness in muscular dystrophy, have not been determined.…”