2590: Growth hormone ameliorates the effects of chronic denervation injury on peripheral nerve regeneration and improves upper extremity murine function

2590: Growth hormone ameliorates the effects of chronic denervation injury on peripheral nerve regeneration and improves upper extremity murine function Joseph Lopez, Amy Quan, Joshua Budihardjo, Kim Sinan, Howard Wang, Chris Cashman, Ahmet Hoke, Sami Tuffaha, W. P. Andrew Lee, and Gerald Brandacher Johns Hopkins University School of Medicine, Vascularized Composite Allotransplantation (VCA) Laboratory, Baltimore, MD, USA 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 D 8) underwent 8 weeks of median nerve CD injury followed by repair; (2) Group 2 animals (experimental, n D 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 D 8) underwent nerve surgery without median nerve CD injury; (4) Group 4 animals (na€ıve positive control, n D 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 D 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 D 005) and decreased CMAP latency (156 § 01 msec vs 270 § 01 msec; P D 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 D 055) when compared to Group 1 at 8 weeks after sciatic nerve CD. Conclusion Systemic GH therapy can maintain chronicallydenervated 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. CONTACT Joseph Lopez jlopez37@jhmi.edu © 2016 Joseph Lopez, Amy Quan, Joshua Budihardjo, Kim Sinan, Howard Wang, Chris Cashman, Ahmet Hoke, Sami Tuffaha, W. P. Andrew Lee, and Gerald Brandacher. Published with license by Taylor & Francis. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted. VASCULARIZED COMPOSITE ALLOTRANSPLANTATION 2016, VOL. 3, NOS. 1–2, 49 http://dx.doi.org/10.1080/23723505.2016.1234254