Effects of nandrolone on recovery after neurotization of chronically denervated muscle in a rat model

Abstract

F unctional recovery following major peripheral nerve injuries is often suboptimal despite appropriate and standard treatment. 2,23,27,34,44 Muscles may be reinnervated but remain too weakened to offer much functional benefit. Although a complex and multifactorial problem, time-related permanent changes to denervated muscle awaiting reinnervation play a significant role in these poor results. This process, referred to as denervation atrophy, involves loss of muscle mass, muscle fiber size, and contractile composition. 16,51 While research has progressed toward ways to improve nerve regeneration and to avoid or decrease the development of these muscle changes, our focus has been on strategies to optimize and augment the functional recovery of reinnervated muscles.Anabolic steroids, which have been shown to cause hypertrophy of normal muscle, delay atrophy in immobilized muscle, and to slow progression of denervation atrophy, 9,45,59 are an obvious candidate for this application. Promising preliminary data demonstrated improved muscle contraction recovery in anabolic steroid-treated rodents following the reversal of chronic denervation of hind limb muscles. 22 The purpose of this study was to confirm and further elucidate the role and mechanism by which anabolic steroids (nandrolone) improve strength and functional recovery in reinnervated muscles followEffects of nandrolone on recovery after neurotization of chronically denervated muscle in a rat model Object. Suboptimal recovery following repair of major peripheral nerves has been partially attributed to denervation atrophy. Administration of anabolic steroids in conjunction with neurotization may improve functional recovery of chronically denervated muscle. The purpose of this study was to evaluate the effect of the administration of nandrolone on muscle recovery following prolonged denervation in a rat model.Methods. Eight groups of female Sprague-Dawley rats (15 rats per group, 120 in all) were divided into 3-or 6-month denervated hind limb and sham surgery groups and, then, nandrolone treatment groups and sham treatment groups. Evaluation of treatment effects included nerve conduction, force of contraction, comparative morphology, histology (of muscle fibers), protein electrophoresis (for muscle fiber grouping), and immunohistochemical evaluation.Results. Although a positive trend was noted, neither reinnervated nor normal muscle showed a statistically significant increase in peak muscle force following nandrolone treatment. Indirect measures, including muscle mass (weight and diameter), muscle cell size, muscle fiber type, and satellite cell counts, all failed to support significant anabolic effect.Conclusions. There does not seem to be a functional benefit from nandrolone treatment following reinnervation of either mild or moderately atrophic muscle (related to prolonged denervation) in a rodent model. (http://thejns.org/doi/abs/10.3171/2013.5.JNS121837) key WorDs • anabolic steroid • denervation atrophy • nerve repair • rodent • muscle recovery • nand...

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