The Use of Anabolic Steroids as a Strategy in Reversing Denervation Atrophy after Delayed Nerve Repair

Abstract

Background Denervation atrophy is one factor contributing to suboptimal motor recovery following major nerve repair. The hypertrophic effects of anabolic steroids may have a potential role in improving reinnervated muscle strength after delayed repair. Methods Forty-five immature female Sprague-Dawley rats underwent three surgeries and final testing. The tibial nerve was transected in the hind limb of the experimental (n=13) and control (n=14) animals and exposed, but not transected in the sham (n=15) group animals. Three months later, once denervation atrophy was established, all transected nerves underwent repair using an autograft from the contralateral limb. After waiting an additional month to allow axonal regeneration to the gastrocnemius muscles, the rodents were implanted with a subcutaneous infusion pump. For the experimental group, nandrolone was administered over the next 30 days via this pump, while the control and sham group pumps were filled with carrier only. Results Final testing, 6 weeks later, showed improved muscle contraction strength in the steroid-treated animals (72% of sham group strength) compared to control animals (57% of sham group strength, p<0.5). A trend towards increased weight and muscle belly diameter in the steroidtreated group was not statistically significant. Conclusions These findings support the potential role of anabolic steroids in improving recovery of atrophic muscle after delayed reinnervation.

Viral vector delivery of follistatin enhances recovery of reinnervated muscle

“…The left sciatic nerve was exposed (biceps femoris semi‐tendinosis muscle splitting approach) and the tibial nerve was transected just past the bifurcation. Nerve ends were separated and buried in muscle (held by a single 10–0 suture) to prevent inadvertent nerve regeneration . Sham denervation groups underwent nerve exposure without transection.…”

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

“…While the difference between the treatment group and controls was statistically significant, hypertrophy could not be demonstrated morphologically or histologically. 22 While these preliminary results were encouraging, our failure to demonstrate a mechanism to account for the increased strength was disturbing and indicated the need for further study to confirm our initial findings and explain the mechanism of action of nandrolone on reinnervated but atrophic muscle.…”

“…12,13,39,56 Based on this promising literature support, a preliminary investigation into the potential role of anabolic steroids in augmenting reinnervated muscle cells was undertaken. 22 Rats treated with nandrolone following reversal of established denervation atrophy regained 72% muscle contraction force (vs 57% for the control group). While the difference between the treatment group and controls was statistically significant, hypertrophy could not be demonstrated morphologically or histologically.…”

“…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.…”

Effect of vascular endothelial growth factor gene therapy on post-traumatic peripheral nerve regeneration and denervation-related muscle atrophy

“…3 As a consequence, the anatomical and functional connections between motoneurons and skeletal muscle fibers are lost inducing a progressive muscle atrophy. 4, 5 If nerve continuity is guaranteed (by surgical repair), the proximal stump of damaged axons can regenerate within the distal nerve stump, reach the denervated muscle and restore functional connection with it. 3 …”