Comparison of Neurotization Versus Nerve Repair in an Animal Model of Chronically Denervated Muscle

Andrew N. Swanson, Scott W. Wolfe, Michael S Khazzam, Joseph Feinberg, John Ehteshami, Stephen Doty

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Purpose: Reinnervation of chronically denervated muscle is clinically unpredictable and poorly understood. Current operative strategies include either direct nerve repair, nerve grafting, nerve transfer, or neurotization. The goal of this study is to compare muscle recovery using microneural repair versus neurotization in a rat model of chronic denervation. Methods: Fifty-eight Sprague-Dawley rats had surgical denervation of the tibialis anterior muscle by transecting the common peroneal nerve. After 0, 8, 12, or 22 weeks of denervation, animals were assigned to either a direct repair or a neurotization cohort. An additional 7 animals were used for a sham cohort, and 7 of the 58 were used as controls. After a 12-week recovery period, animals had contractile strength and EMG testing of the tibialis anterior muscle. Peak force and characteristics were compared to the unoperated, contralateral limb. Tibialis anterior muscles were then harvested for mass and histologic evaluation. Results: Sixty-two animals completed testing. Denervated controls demonstrated a significant decrease in muscle mass, contractile strength, and peak motor nerve conduction amplitude compared to sham animals. In all groups, chronicity of denervation adversely affected functional recovery. On average, repair animals performed better than neurotization animals with respect to muscle mass, contractile strength, and peak motor amplitude. Differences in contractile force, however, were significant only at the 0 week denervation group (94% ± 30 vs 50% ± 20, repair vs neurotization). Neurotized muscles processed for histologic analysis demonstrated acetylcholinesterase activity at the nerve-muscle interface, confirming the formation of motor end plates de novo. Conclusions: We demonstrated that neurotization is capable of reinnervating de novo end plates in chronically denervated muscle. Our data do not support the hypothesis that direct muscle neurotization is superior to nerve repair for functional restoration of chronically denervated muscle. However, as the duration of denervation increases, the difference between outcomes of the neurotization and repair group narrows, suggesting that neurotization may offer a viable surgical alternative in the setting of prolonged denervation.

Original languageEnglish (US)
Pages (from-to)1093-1099
Number of pages7
JournalJournal of Hand Surgery
Volume33
Issue number7
DOIs
StatePublished - Sep 2008

Fingerprint

Nerve Transfer
Animal Models
Muscles
Denervation
Motor Endplate
Peroneal Nerve
Neural Conduction
Acetylcholinesterase
Sprague Dawley Rats

Keywords

  • Chronic denervation
  • motor end plate
  • rat model
  • reinnervation

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Surgery

Cite this

Comparison of Neurotization Versus Nerve Repair in an Animal Model of Chronically Denervated Muscle. / Swanson, Andrew N.; Wolfe, Scott W.; Khazzam, Michael S; Feinberg, Joseph; Ehteshami, John; Doty, Stephen.

In: Journal of Hand Surgery, Vol. 33, No. 7, 09.2008, p. 1093-1099.

Research output: Contribution to journalArticle

Swanson, Andrew N. ; Wolfe, Scott W. ; Khazzam, Michael S ; Feinberg, Joseph ; Ehteshami, John ; Doty, Stephen. / Comparison of Neurotization Versus Nerve Repair in an Animal Model of Chronically Denervated Muscle. In: Journal of Hand Surgery. 2008 ; Vol. 33, No. 7. pp. 1093-1099.
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abstract = "Purpose: Reinnervation of chronically denervated muscle is clinically unpredictable and poorly understood. Current operative strategies include either direct nerve repair, nerve grafting, nerve transfer, or neurotization. The goal of this study is to compare muscle recovery using microneural repair versus neurotization in a rat model of chronic denervation. Methods: Fifty-eight Sprague-Dawley rats had surgical denervation of the tibialis anterior muscle by transecting the common peroneal nerve. After 0, 8, 12, or 22 weeks of denervation, animals were assigned to either a direct repair or a neurotization cohort. An additional 7 animals were used for a sham cohort, and 7 of the 58 were used as controls. After a 12-week recovery period, animals had contractile strength and EMG testing of the tibialis anterior muscle. Peak force and characteristics were compared to the unoperated, contralateral limb. Tibialis anterior muscles were then harvested for mass and histologic evaluation. Results: Sixty-two animals completed testing. Denervated controls demonstrated a significant decrease in muscle mass, contractile strength, and peak motor nerve conduction amplitude compared to sham animals. In all groups, chronicity of denervation adversely affected functional recovery. On average, repair animals performed better than neurotization animals with respect to muscle mass, contractile strength, and peak motor amplitude. Differences in contractile force, however, were significant only at the 0 week denervation group (94{\%} ± 30 vs 50{\%} ± 20, repair vs neurotization). Neurotized muscles processed for histologic analysis demonstrated acetylcholinesterase activity at the nerve-muscle interface, confirming the formation of motor end plates de novo. Conclusions: We demonstrated that neurotization is capable of reinnervating de novo end plates in chronically denervated muscle. Our data do not support the hypothesis that direct muscle neurotization is superior to nerve repair for functional restoration of chronically denervated muscle. However, as the duration of denervation increases, the difference between outcomes of the neurotization and repair group narrows, suggesting that neurotization may offer a viable surgical alternative in the setting of prolonged denervation.",
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T1 - Comparison of Neurotization Versus Nerve Repair in an Animal Model of Chronically Denervated Muscle

AU - Swanson, Andrew N.

AU - Wolfe, Scott W.

AU - Khazzam, Michael S

AU - Feinberg, Joseph

AU - Ehteshami, John

AU - Doty, Stephen

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N2 - Purpose: Reinnervation of chronically denervated muscle is clinically unpredictable and poorly understood. Current operative strategies include either direct nerve repair, nerve grafting, nerve transfer, or neurotization. The goal of this study is to compare muscle recovery using microneural repair versus neurotization in a rat model of chronic denervation. Methods: Fifty-eight Sprague-Dawley rats had surgical denervation of the tibialis anterior muscle by transecting the common peroneal nerve. After 0, 8, 12, or 22 weeks of denervation, animals were assigned to either a direct repair or a neurotization cohort. An additional 7 animals were used for a sham cohort, and 7 of the 58 were used as controls. After a 12-week recovery period, animals had contractile strength and EMG testing of the tibialis anterior muscle. Peak force and characteristics were compared to the unoperated, contralateral limb. Tibialis anterior muscles were then harvested for mass and histologic evaluation. Results: Sixty-two animals completed testing. Denervated controls demonstrated a significant decrease in muscle mass, contractile strength, and peak motor nerve conduction amplitude compared to sham animals. In all groups, chronicity of denervation adversely affected functional recovery. On average, repair animals performed better than neurotization animals with respect to muscle mass, contractile strength, and peak motor amplitude. Differences in contractile force, however, were significant only at the 0 week denervation group (94% ± 30 vs 50% ± 20, repair vs neurotization). Neurotized muscles processed for histologic analysis demonstrated acetylcholinesterase activity at the nerve-muscle interface, confirming the formation of motor end plates de novo. Conclusions: We demonstrated that neurotization is capable of reinnervating de novo end plates in chronically denervated muscle. Our data do not support the hypothesis that direct muscle neurotization is superior to nerve repair for functional restoration of chronically denervated muscle. However, as the duration of denervation increases, the difference between outcomes of the neurotization and repair group narrows, suggesting that neurotization may offer a viable surgical alternative in the setting of prolonged denervation.

AB - Purpose: Reinnervation of chronically denervated muscle is clinically unpredictable and poorly understood. Current operative strategies include either direct nerve repair, nerve grafting, nerve transfer, or neurotization. The goal of this study is to compare muscle recovery using microneural repair versus neurotization in a rat model of chronic denervation. Methods: Fifty-eight Sprague-Dawley rats had surgical denervation of the tibialis anterior muscle by transecting the common peroneal nerve. After 0, 8, 12, or 22 weeks of denervation, animals were assigned to either a direct repair or a neurotization cohort. An additional 7 animals were used for a sham cohort, and 7 of the 58 were used as controls. After a 12-week recovery period, animals had contractile strength and EMG testing of the tibialis anterior muscle. Peak force and characteristics were compared to the unoperated, contralateral limb. Tibialis anterior muscles were then harvested for mass and histologic evaluation. Results: Sixty-two animals completed testing. Denervated controls demonstrated a significant decrease in muscle mass, contractile strength, and peak motor nerve conduction amplitude compared to sham animals. In all groups, chronicity of denervation adversely affected functional recovery. On average, repair animals performed better than neurotization animals with respect to muscle mass, contractile strength, and peak motor amplitude. Differences in contractile force, however, were significant only at the 0 week denervation group (94% ± 30 vs 50% ± 20, repair vs neurotization). Neurotized muscles processed for histologic analysis demonstrated acetylcholinesterase activity at the nerve-muscle interface, confirming the formation of motor end plates de novo. Conclusions: We demonstrated that neurotization is capable of reinnervating de novo end plates in chronically denervated muscle. Our data do not support the hypothesis that direct muscle neurotization is superior to nerve repair for functional restoration of chronically denervated muscle. However, as the duration of denervation increases, the difference between outcomes of the neurotization and repair group narrows, suggesting that neurotization may offer a viable surgical alternative in the setting of prolonged denervation.

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KW - rat model

KW - reinnervation

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