Neuromuscular interaction is required for neurotrophins-mediated locomotor recovery following treadmill training in rat spinal cord injury

PeerJ. 2016 May 11:4:e2025. doi: 10.7717/peerj.2025. eCollection 2016.

Abstract

Recent results have shown that exercise training promotes the recovery of injured rat distal spinal cords, but are still unclear about the function of skeletal muscle in this process. Herein, rats with incomplete thoracic (T10) spinal cord injuries (SCI) with a dual spinal lesion model were subjected to four weeks of treadmill training and then were treated with complete spinal transection at T8. We found that treadmill training allowed the retention of hind limb motor function after incomplete SCI, even with a heavy load after complete spinal transection. Moreover, treadmill training alleviated the secondary injury in distal lumbar spinal motor neurons, and enhanced BDNF/TrkB expression in the lumbar spinal cord. To discover the influence of skeletal muscle contractile activity on motor function and gene expression, we adopted botulinum toxin A (BTX-A) to block the neuromuscular activity of the rat gastrocnemius muscle. BTX-A treatment inhibited the effects of treadmill training on motor function and BDNF/TrKB expression. These results indicated that treadmill training through the skeletal muscle-motor nerve-spinal cord retrograde pathway regulated neuralplasticity in the mammalian central nervous system, which induced the expression of related neurotrophins and promoted motor function recovery.

Keywords: BDNF; Motor neurons; Neuromuscular activity; Neurotrophins; Spinal cord injury; Treadmill training.

Grants and funding

This study was supported with grants from the National Natural Science Foundation of China (81171851, 81000853, 81501189, 81472163), The Open Foundation of the Department of Rehabilitation Medicine of Jiangsu Province Hospital (XK201110), Affiliated Hospital of Nantong University Foundation (TDFY0313), the Natural Science Foundation of Jiangsu Higher Education Institutions (15KJB180014, 11KJB180010), and the Application Research Project of Nantong City (Grant Nos. MS2015097). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.