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

Publication date: Available online 21 December 2018

Source: The Spine Journal

Author(s): Norito Hayashi, Naoyuki Himi, Emi Nakamura-Maruyama, Naohiko Okabe, Issei Sakamoto, Toru Hasegawa, Osamu Miyamoto

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 min) 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 (BBB) Locomotor Scale, inclined plane test, and rotarod test. One week after injury, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-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 (pGAP43) in the spinal cord were measured.

RESULTS

Significantly improved BBB scores and inclined plane test results were observed in the SCI+ES group compared to those in the SCI group at 4 weeks post-SCI. We also observed a decrease in the cavity volume and an increase in pGAP43 levels in the SCI+ES group. Electrical muscle stimulation decreased the numbers of TUNEL-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.

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