Regenerative responses in slow- and fast-twitch muscles following moderate contusion spinal cord injury and locomotor training

Abstract

The aim of this study was to use the rat moderate spinal cord contusion model to investigate the effects of incomplete spinal cord injury (SCI) on the muscle regeneration process, comparing regeneration of slow-twitch plantarflexor soleus muscle and fast-twitch dorsiflexor tibialis anterior (TA) muscle. Additionally, we wanted to examine the effect of a week of locomotor training following incomplete SCI on the muscle regeneration process in these muscles and also determine if a week of similar locomotor training is sufficient to initiate muscle regeneration in control, non-injured rats. Thirty-two, adult, female, Sprague-Dawley rats were chosen for the study. Moderate, midthoracic contusion SCIs were produced using a NYU (New York University) impactor in all rats except controls. Animals were randomly assigned to treadmill training or untrained groups. Rats in the treadmill training group were manually treadmill trained starting at 1 week after SCI, for 10 bouts (2 sessions of 20 min of actual stepping) over 5 days and control rats in the training group received similar training. Our results indicate that a muscle regenerative response was initiated only in the slow-twitch soleus muscle in the initial 2 weeks following SCI, the addition of 1 week of locomotor treadmill training led to a significant increase in soleus regenerative process. No significant regenerative process was observed in the fast-twitch TA. Increased muscle regeneration in soleus is suggested by our findings of increased expression of (1) insulin-like growth factor-1, involved in the activation of satellite cells; (2) Pax7, a marker of satellite cell activation; (3) myogenin, a muscle regulatory protein; and (4) embryonic myosin, an indicator of new muscle fiber formation. Locomotor training in control, non-injured animals did not induce similar changes towards the regenerative process.