Improvement of motor function induced by skeletal muscle contraction in spinal cord-injured rats

Abstract

Background: The involvement of neurotrophic factors such as brain-derived neurotrophic factor (BDNF) in functional recovery after spinal cord injury (SCI) by treadmill training has been suggested. The precise mechanism is poorly understood. However, muscle-derived bioactive molecules (myokines) are known to be produced by muscle contraction. Although BDNF is a myokine and is considered to be a potential mediator of neuroplasticity following exercise, its contribution to motor function recovery after SCI has not yet been described in detail.

Purpose: To investigate the role of muscle contraction in motor function recovery after SCI, with a focus on BDNF.

Study design: Male Sprague-Dawley rats (aged 8-9 weeks) were used to establish the SCI model. Percutaneous electrical muscle stimulation (10 mA, 2 Hz, 10 minutes) was applied to both hindlimbs of the rats immediately after SCI. The stimulation was performed once per day for 4 weeks. The sham, SCI only (SCI), and SCI with electrical muscle stimulation (SCI+ES) groups were compared.

Methods: Spinal cord injury was induced by dropping a 20 g rod with an apex diameter of 2 mm from a height of 25 mm onto the spine of an anesthetized rat at the T9 level. Motor function was assessed using the Basso-Beattie-Bresnahan Locomotor Scale, inclined plane test, and rotarod test. One week after injury, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells were counted at the injury epicenter, and the level of BDNF was measured in both the spinal cord and the anterior tibial muscle. Four weeks after injury, the cavity volume of the epicenter and the level of phosphorylated growth-associated protein 43 in the spinal cord were measured.

Results: Significantly improved Basso-Beattie-Bresnahan scores and inclined plane test results were observed in the SCI+ES group compared with those in the SCI group at 4 weeks post-SCI. We also observed a decrease in the cavity volume and an increase in phosphorylated growth-associated protein 43 levels in the SCI+ES group. Electrical muscle stimulation decreased the numbers of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells in the epicenter and increased the levels of BDNF in the spinal cord and lower limb muscles at 1 week post-SCI.

Conclusions: Electrical muscle stimulation improved motor function and increased BDNF levels in both the muscles and the spinal cords of rats subjected to SCI. Muscle contraction-induced BDNF expression might be involved in motor recovery during rehabilitation.

Clinical relevance: Our study provides experimental evidence for a possible therapeutic role of peripheral electrical muscle stimulation to enhance motor recovery after SCI.

Keywords: Brain-derived neurotrophic factor (BDNF); Electrical stimulation; Motor function recovery; Muscle contraction; Myokines; Spinal cord injury.