%0 Journal Article %T Molecular Mechanisms of Treadmill Therapy on Neuromuscular Atrophy Induced via Botulinum Toxin A %A Sen-Wei Tsai %A Hsiao-Ling Chen %A Yi-Chun Chang %A Chuan-Mu Chen %J Neural Plasticity %D 2013 %I Hindawi Publishing Corporation %R 10.1155/2013/593271 %X Botulinum toxin A (BoNT-A) is a bacterial zinc-dependent endopeptidase that acts specifically on neuromuscular junctions. BoNT-A blocks the release of acetylcholine, thereby decreasing the ability of a spastic muscle to generate forceful contraction, which results in a temporal local weakness and the atrophy of targeted muscles. BoNT-A-induced temporal muscle weakness has been used to manage skeletal muscle spasticity, such as poststroke spasticity, cerebral palsy, and cervical dystonia. However, the combined effect of treadmill exercise and BoNT-A treatment is not well understood. We previously demonstrated that for rats, following BoNT-A injection in the gastrocnemius muscle, treadmill running improved the recovery of the sciatic functional index (SFI), muscle contraction strength, and compound muscle action potential (CMAP) amplitude and area. Treadmill training had no influence on gastrocnemius mass that received BoNT-A injection, but it improved the maximal contraction force of the gastrocnemius, and upregulation of GAP-43, IGF-1, Myo-D, Myf-5, myogenin, and acetylcholine receptor (AChR) subunits ¦Á and ¦Â was found following treadmill training. Taken together, these results suggest that the upregulation of genes associated with neurite and AChR regeneration following treadmill training may contribute to enhanced gastrocnemius strength recovery following BoNT-A injection. 1. Introduction Treadmill exercise, both full weight-bearing and partial weight-bearing, is a dynamic training approach that provides intervention for walking and gait analysis. In patients with neuromuscular disorders, such as stroke, spinal cord injury (SCI), or cerebral palsy (CP), treadmill exercise is a frequently used rehabilitation training model that has been shown to yield functional improvements [1¨C4]. Clinical investigations showed that in patients with CP, treadmill training can improve walking endurance, walking speed, and standing performance [5, 6]. In stroke rehabilitation, partial-support treadmill training is also a widely used training mode for gait correction [7, 8]. Spasticity is a sign of upper motor neuron lesion with increased stretch reflex depending on movement velocity, which can be caused by stroke, spinal cord injury, brain injury, cerebral palsy, or other neurological conditions [9]. One of the treatment choices for spasticity is the intramuscular injection of botulinum toxin A (BoNT-A) [10, 11]. Although several studies support the beneficial effects of treadmill training, most excluded BoNT-A-treated patients or did not mention these patients [12¨C14]. %U http://www.hindawi.com/journals/np/2013/593271/