Abstract
This study investigates the efficacy of systemic growth hormone (GH) therapy in ameliorating the deleterious effects of chronic denervation (CD) injury on nerve regeneration and resulting motor function. Using a forelimb CD model, 4 groups of Lewis rats were examined (n = 8 per group): Group-1 (negative control) 8 weeks of median nerve CD followed by ulnar-to-median nerve transfer; Group-2 (experimental) 8 weeks of median nerve CD followed by ulnar-to-median nerve transfer and highly purified lyophilized pituitary porcine GH treatment (0.6 mg/day); Group-3 (positive control) immediate ulnar-to-median nerve transfer without CD; Group-4 (baseline) naïve controls. All animals underwent weekly grip strength testing and were sacrificed 14 weeks following nerve transfer for histomorphometric analysis of median nerve regeneration, flexor digitorum superficialis atrophy, and neuromuscular junction reinnervation. In comparison to untreated controls, GH-treated animals demonstrated enhanced median nerve regeneration as measured by axon density (p < 0.005), axon diameter (p < 0.0001), and myelin thickness (p < 0.0001); improved muscle re-innervation (27.9% vs 38.0% NMJs re-innervated; p < 0.02); reduced muscle atrophy (1146 ± 93.19 µm2 vs 865.2 ± 48.33 µm2; p < 0.02); and greater recovery of motor function (grip strength: p < 0.001). These findings support the hypothesis that GH-therapy enhances axonal regeneration and maintains chronically-denervated muscle to thereby promote motor re-innervation and functional recovery.
Highlights
IGF-1 has been shown to markedly reduce the rate of denervation-induced muscle atrophy[15,16,17] and stimulate axonal sprouting into denervated muscle during the process of reinnervation[18]
This study is the first to assess the effects of growth hormone (GH) therapy in a model in which chronic denervation is induced prior to nerve repair
Because the regenerative distances in rat nerve injury models are very short relative to those seen in humans, axons will reach their targets before the effects of prolonged denervation can take place
Summary
IGF-1 has been shown to markedly reduce the rate of denervation-induced muscle atrophy[15,16,17] and stimulate axonal sprouting into denervated muscle during the process of reinnervation[18]. A model in which chronic denervation is induced prior to nerve repair is needed to fully assess the hypothesized multi-modal mechanism of action of GH therapy involving maintenance of denervated muscle and SCs, in addition to direct neurotrophic effects on regenerating axons. We used a rat median nerve chronic denervation (CD) model to investigate the ability of GH therapy to reduce denervation-induced muscle atrophy and SC senescence, enhance axonal regeneration and muscle re-innervation, and thereby improve functional recovery
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
