Introduction
It is well understood that peripheral nerve regeneration is pivotal to facilitate graft function after VCA Therefore, exploring therapies that enhance this process can dramatically improve outcomes The purpose of this study was to assess the impact of growth hormone (GH) therapy on preventing the deleterious effects of chronic denervation (CD) injury on peripheral nerve regeneration and resulting extremity function.
Methods
We utilized a rat CD model to assess the effects of GH therapy on: a) maintaining denervated muscle and SCs, and b) functional recovery in the setting of CD Four groups of Lewis rats were examined: (1) Group 1 animals (negative control, n = 8) underwent 8 weeks of median nerve CD injury followed by repair; (2) Group 2 animals (experimental, n = 8) underwent 8 weeks of median nerve CD followed by repair and treatment with highly purified lyophilized pituitary porcine GH (06 mg/day); (3) Group 3 animals (positive control, n = 8) underwent nerve surgery without median nerve CD injury; (4) Group 4 animals (naïve positive control, n = 8) underwent no nerve surgery All groups underwent weekly functional and CMAP testing for 14 weeks post-nerve repair.
Results
Group 2 rats demonstrated statistically significant greater functional recovery as compared to Group 1 rats (Hand grip: 18 ± 03 N vs 10 ± 01 N, P = 0001) at the study endpoint At 12 weeks post-median nerve repair, Group 2 rats demonstrated higher median nerve CMAP amplitude (087 ± 017 millivolts vs 048 ± 01 millivolts; P = 005) and decreased CMAP latency (156 ± 01 msec vs 270 ± 01 msec; P = 054), suggestive of improved median nerve regeneration as compared to Group 1 rats Lastly, Group 2 animals demonstrated higher expression of SC proliferation and migration markers, c-Jun and erbB-3, and less muscle atrophy (021 ± 002 g vs 017 ± 001 g; P = 055) when compared to Group 1 at 8 weeks after sciatic nerve CD.
Conclusion
Systemic GH therapy can maintain chronically-denervated muscle and Schwann cells and improve extremity function in the setting of CD Therefore, future studies should explore whether GH therapy can augment functional outcomes after VCA.