Molecular Mechanisms of Treadmill Therapy on Neuromuscular Atrophy Induced via Botulinum Toxin A

Abstract

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 α and β 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.

Changes of Plantar Pressure and Gait Parameters in Children with Mild Cerebral Palsy Who Used a Customized External Strap Orthosis: A Crossover Study

“…Treadmills are devices often used not only as a gait evaluation tool but also as rehabilitation training tools for patients with stroke, spinal cord injuries, and cerebral palsy [ 31 ]. Previous study showed that children with cerebral palsy can improve their walking distance, speed, and standing posture by treadmill training [ 22 ].…”

“…In addition, the walking speed and distance can be controlled freely in accordance with the children or environment requirements. Moreover, the treadmill makes it possible for children to continue ongoing activities during the time of the operation, which is convenient for researchers to collect gait parameters [ 31 ]. The disadvantage is that the muscles of lower extremity may be passively driven by treadmill motor.…”

“…In addition, the treadmill is relatively flat-surfaced and stable and is different from uneven ground [ 32 ]. Therefore, it is easier for the children to control their balance on treadmills [ 31 , 32 ]. Gait strategy on a treadmill is different from that on the ground, and, consequently, generalization on the ambulation skill learning transfer from walking on a treadmill to walking on the ground is difficult for the disabled.…”

Comparison of neurotoxic potency between a novel chinbotulinumtoxinA with onabotulinumtoxinA, incobotulinumtoxinA and lanbotulinumtoxinA in rats

“…Gradually, wear-off of toxins and recovery of muscle function might imply that some compensative mechanisms exist to counteract the action of toxins upon injection. Studies have confirmed that BoNT/A injection could effectively induce muscle paralysis, followed by a profile of gene transcription changes leading to muscle recovery 28,32. Two stages may be involved in this rehabilitation process: an early aneural stage and a later neural stage.…”

Recuperação funcional após aplicação de toxina abobotulínica A no músculo gastrocnêmio contralateral ao reparo do nervo tibial em ratos

“…O objetivo do presente estudo foi avaliar a recuperação funcional em ratos submetidos à lesão e reparo do nervo tibial após a injeção de 5 U de toxina abobotulínicia tipo A no músculo gastrocnêmio contralateral. A dose foi padronizada a partir da revisão de estudos prévios que utilizaram a toxina onabotulínica A e abobotulínica A no músculo gastrocnêmio de ratos (Cichon et al, 1995;Chen et al, 2002a;Ma et al, MÉTODOS -13 2004;Rosales et al, 2006;Velders et al, 2008;Legerlotz et al, 2009;Stone et al, 2011b;Han et al, 2013;Tsai et al, 2013;Akdeniz et al, 2015).…”