Force Deficits in Skeletal Muscle after Delayed Reinnervation

Aydın, Mustafa Asım; Mackinnon, Susan E.; Gu, Xiaoa Ming; Kobayashi, Jun; Kuzon, William M.

doi:10.1097/01.prs.0000118049.93654.ca

Cited by 66 publications

(66 citation statements)

References 28 publications

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“…Indirect measures of reinnervation following nerve injury include gauging muscle force and power production and assessing functional recovery using walking track analysis (Aydin, et al, 2004, Cederna, et al, 2000, Kobayashi, et al, 1997, Yoshimura, et al, 1999, Yoshimura, et al, 2002. These indirect measures of functional recovery, however, have limited sensitivity and vary not only with motor endplate reinnervation, but with cortical control of limb movement, post-operative stiffness, and the influences of a learning curve (Dellon andMackinnon, 1989, Nichols, et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Reinnervation of the tibialis anterior following sciatic nerve crush injury: A confocal microscopic study in transgenic mice

Magill

Tong

Kawamura

et al. 2007

Experimental Neurology

108

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Transgenic mice whose axons and Schwann cells express fluorescent chromophores enable new imaging techniques and augment concepts in developmental neurobiology. The utility of these tools in the study of traumatic nerve injury depends on employing nerve models that are amenable to microsurgical manipulation and gauging functional recovery. Motor recovery from sciatic nerve crush injury is studied here by evaluating motor endplates of the tibialis anterior muscle, which is innervated by the deep peroneal branch of the sciatic nerve. Following sciatic nerve crush, the deep surface of the tibialis anterior muscle is examined using whole mount confocal microscopy, and reinnervation is characterized by imaging fluorescent axons or Schwann cells (SCs). One week following sciatic crush injury, 100% of motor endplates are denervated with partial reinnervation at two weeks, hyperinnervation at three and four weeks, and restoration of a 1:1 axon to motor endplate relationship six weeks after injury. Walking track analysis reveals progressive recovery of sciatic nerve function by six weeks. SCs reveal reduced S100 expression within two weeks of denervation, correlating with regression to a more immature phenotype. Reinnervation of SCs restores S100 expression and a fully differentiated phenotype. Following denervation, there is altered morphology of circumscribed terminal Schwann cells demonstrating extensive process formation between adjacent motor endplates. The thin, uniformly innervated tibialis anterior muscle is well suited for studying motor reinnervation following sciatic nerve injury. Confocal microscopy may be performed coincident with other techniques of assessing nerve regeneration and functional recovery.

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Section: Introductionmentioning

confidence: 99%

Reinnervation of the tibialis anterior following sciatic nerve crush injury: A confocal microscopic study in transgenic mice

Magill

Tong

Kawamura

et al. 2007

Experimental Neurology

108

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“…Despite advances in our understanding of nerve regeneration, treatment outcomes have not seen an equivalent improvement [2,26,29,36,42]. Indeed, the literature demonstrates too many "almost good" results following major nerve repairs.…”

Section: Discussionmentioning

confidence: 99%

“…Functional motor recovery following repair of major peripheral nerve injuries is often suboptimal [2,26,29,36,42]. The explanation for this is multifactorial, but delays in muscle reinnervation associated with long regeneration lengths or delayed surgical intervention negatively affects both muscle and nerve recovery potential [17].…”

Section: Introductionmentioning

confidence: 99%

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

Isaacs

Loveland

Mallu

et al. 2011

Hand (New York, N,Y.)

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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.

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“…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.…”

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confidence: 99%

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

Isaacs¹,

Feher²,

Shall³

et al. 2013

JNS

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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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Force Deficits in Skeletal Muscle after Delayed Reinnervation

Cited by 66 publications

References 28 publications

Reinnervation of the tibialis anterior following sciatic nerve crush injury: A confocal microscopic study in transgenic mice

Reinnervation of the tibialis anterior following sciatic nerve crush injury: A confocal microscopic study in transgenic mice

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

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

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