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

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.

Blocking of BDNF-TrkB signaling inhibits the promotion effect of neurological function recovery after treadmill training in rats with spinal cord injury

“…After 7 days of intrathecal catheter, all rats were administered analgesic and anesthesia as above. The New York University (NYU) Impactor System is the modified Allen's method that was employed to establish a T10 incomplete SCI model by dropping a device rod (10 g) from a vertical distance of 2.5 cm onto the exposed spinal cord [15,18]. The Sham group only exposed the T10 spinal cord.…”

“…The TT began at 8 days post SCI and was conducted for 5 days/week and 2 times/day for 4 consecutive weeks [15]. The exercise training was performed for 20 min each time based on the body weight supported TT.…”

“…The Nissl staining was used to observe the cell body area of motor neurons and morphological characteristics after SCI [15]. The L2-L5 spinal cord sections of all rats were deparaffinized and rehydrated, placed in cresyl violet for 30 min, and then, washed by running water, 95% alcohol for 2 s, dehydrated, turned transparent, and mounted in neutral gums.…”

“…The recovery of motor function in untrained SCI rats might be related to the spontaneous recovery of central model generator (CPG) [15]. After exercise training, the conduction of corticospinal tract, CPG recovery, and synaptic plasticity might further improve the motor function.…”

“…BDNF is involved in repairing the damaged spinal cord via activation of the specific receptor tropomyosin-related kinase B (TrkB) [13,14]. Our previous study found that exercise training promotes the expression of BDNF and TrkB in the distal spinal cord and the recovery of locomotor function in rats with SCI [15]. However, whether the exercise-induced increased level of BDNF is essential in SCI functional recovery and neuroplasticity is yet unclear.…”