Growth Hormone Therapy Accelerates Axonal Regeneration, Promotes Motor Reinnervation, and Reduces Muscle Atrophy following Peripheral Nerve Injury

Background: Therapies to improve outcomes following peripheral nerve injury are lacking. Prolonged denervation of muscle and Schwann cells contributes to poor outcomes. In this study, the authors assess the effects of growth hormone therapy on axonal regeneration, Schwann cell and muscle maintenance, and end-organ reinnervation in rats. Methods: Male Sprague-Dawley rats underwent sciatic nerve transection and repair and femoral nerve transection without repair and received either daily subcutaneous growth hormone (0.4 mg/day) or no treatment (n = 8 per group). At 5 weeks, the authors assessed axonal regeneration within the sciatic nerve, muscle atrophy within the gastrocnemius muscle, motor endplate reinnervation within the soleus muscle, and Schwann cell proliferation within the denervated distal femoral nerve. Results: Growth hormone-treated animals demonstrated greater percentage increase in body mass (12.2 +/- 1.8 versus 8.5 +/- 1.5; p = 0.0044), greater number of regenerating myelinated axons (13,876 +/- 2036 versus 8645 +/- 3279; p = 0.0018) and g-ratio (0.64 +/- 0.11 versus 0.51 +/- 0.06; p = 0.01), greater percentage reinnervation of motor endplates (75.8 +/- 8.7 versus 38.2 +/- 22.6; p = 0.0008), and greater muscle myofibril cross-sectional area (731.8 +/- 157 mu m versus 545.2 +/- 144.3 mu m; p = 0.027). Conclusions: In male rats, growth hormone therapy accelerates axonal regeneration, reduces muscle atrophy, and promotes muscle reinnervation. Growth hormone therapy may also maintain proliferating Schwann cells in the setting of prolonged denervation. These findings suggest potential for improved outcomes with growth hormone therapy after peripheral nerve injuries.