Comparison between neurectomy and botulinum toxin A injection for denervated skeletal muscle

Feng-Chou Tsai, Ming-Shium Hsieh, Chih Ming Chou

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Neurectomy and botulinum toxin A (BoNT-A) injection cause denervated muscle atrophy, but questions remain about their clinical utility. We investigated time-series alterations of rat muscle weight, functional deficits, signaling pathways, and microscopic structures, to gain an understanding of the clinical implications. Between 2008 and 2009, the maximal calf circumference of patients for calf reduction either by neurectomy or BoNT-A injections were recorded for study. A rat skeletal muscle model was established through repeated or dose-adjusted BoNT-A injections and neurectomy. The survival, apoptosis pathways, functional deficits, and microscopic structures were investigated using Western blot, sciatic functional index (SFI), and transmission electron microscopy (TEM), respectively. The rat muscle weight ratio of the BoNT-A group had recovered to 89.3 ± 3.8% by week 58, but it never recovered in the neurectomy group. Muscle weight reduction by BoNT-A not only depended on the dose, but additive effects were also obtained through repeated injections. Rat SFI demonstrated rapid recovery in both groups. Molecular expressions showed a coherent and biphasic pattern. p-Akt and apoptosis-inducing factor (AIF) were upregulated significantly, with a peak at 8 weeks in the neurectomy group (p <0.01), but cleaved caspase-9 and caspase-3 showed no significant changes in either group. TEM findings showed irreversible and reversible inner-structure disruption and sarcomere discontinuity in the neurectomy and BoNT-A groups, respectively. We demonstrated that denervation induced lasting muscle weight and structural changes of different degrees. Muscle weight reduction by BoNT-A was related to frequency and dose. AIF-mediated caspase-independent apoptosis was significantly different for neurectomy and BoNT-A injection.

Original languageEnglish
Pages (from-to)1509-1516
Number of pages8
JournalJournal of Neurotrauma
Volume27
Issue number8
DOIs
Publication statusPublished - Aug 1 2010

Fingerprint

Type A Botulinum Toxins
Skeletal Muscle
Injections
Muscles
Apoptosis Inducing Factor
Transmission Electron Microscopy
Weights and Measures
Weight Loss
Apoptosis
Sarcomeres
Muscular Atrophy
Caspase 9
Denervation
Caspases
Caspase 3
Western Blotting
Survival

Keywords

  • apoptosis
  • botulinum toxin
  • denervation
  • neurectomy
  • skeletal muscle

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Comparison between neurectomy and botulinum toxin A injection for denervated skeletal muscle. / Tsai, Feng-Chou; Hsieh, Ming-Shium; Chou, Chih Ming.

In: Journal of Neurotrauma, Vol. 27, No. 8, 01.08.2010, p. 1509-1516.

Research output: Contribution to journalArticle

@article{768ed441d72a4b458eceb05f036bbe9d,
title = "Comparison between neurectomy and botulinum toxin A injection for denervated skeletal muscle",
abstract = "Neurectomy and botulinum toxin A (BoNT-A) injection cause denervated muscle atrophy, but questions remain about their clinical utility. We investigated time-series alterations of rat muscle weight, functional deficits, signaling pathways, and microscopic structures, to gain an understanding of the clinical implications. Between 2008 and 2009, the maximal calf circumference of patients for calf reduction either by neurectomy or BoNT-A injections were recorded for study. A rat skeletal muscle model was established through repeated or dose-adjusted BoNT-A injections and neurectomy. The survival, apoptosis pathways, functional deficits, and microscopic structures were investigated using Western blot, sciatic functional index (SFI), and transmission electron microscopy (TEM), respectively. The rat muscle weight ratio of the BoNT-A group had recovered to 89.3 ± 3.8{\%} by week 58, but it never recovered in the neurectomy group. Muscle weight reduction by BoNT-A not only depended on the dose, but additive effects were also obtained through repeated injections. Rat SFI demonstrated rapid recovery in both groups. Molecular expressions showed a coherent and biphasic pattern. p-Akt and apoptosis-inducing factor (AIF) were upregulated significantly, with a peak at 8 weeks in the neurectomy group (p <0.01), but cleaved caspase-9 and caspase-3 showed no significant changes in either group. TEM findings showed irreversible and reversible inner-structure disruption and sarcomere discontinuity in the neurectomy and BoNT-A groups, respectively. We demonstrated that denervation induced lasting muscle weight and structural changes of different degrees. Muscle weight reduction by BoNT-A was related to frequency and dose. AIF-mediated caspase-independent apoptosis was significantly different for neurectomy and BoNT-A injection.",
keywords = "apoptosis, botulinum toxin, denervation, neurectomy, skeletal muscle",
author = "Feng-Chou Tsai and Ming-Shium Hsieh and Chou, {Chih Ming}",
year = "2010",
month = "8",
day = "1",
doi = "10.1089/neu.2010.1320",
language = "English",
volume = "27",
pages = "1509--1516",
journal = "Journal of Neurotrauma",
issn = "0897-7151",
publisher = "Mary Ann Liebert Inc.",
number = "8",

}

TY - JOUR

T1 - Comparison between neurectomy and botulinum toxin A injection for denervated skeletal muscle

AU - Tsai, Feng-Chou

AU - Hsieh, Ming-Shium

AU - Chou, Chih Ming

PY - 2010/8/1

Y1 - 2010/8/1

N2 - Neurectomy and botulinum toxin A (BoNT-A) injection cause denervated muscle atrophy, but questions remain about their clinical utility. We investigated time-series alterations of rat muscle weight, functional deficits, signaling pathways, and microscopic structures, to gain an understanding of the clinical implications. Between 2008 and 2009, the maximal calf circumference of patients for calf reduction either by neurectomy or BoNT-A injections were recorded for study. A rat skeletal muscle model was established through repeated or dose-adjusted BoNT-A injections and neurectomy. The survival, apoptosis pathways, functional deficits, and microscopic structures were investigated using Western blot, sciatic functional index (SFI), and transmission electron microscopy (TEM), respectively. The rat muscle weight ratio of the BoNT-A group had recovered to 89.3 ± 3.8% by week 58, but it never recovered in the neurectomy group. Muscle weight reduction by BoNT-A not only depended on the dose, but additive effects were also obtained through repeated injections. Rat SFI demonstrated rapid recovery in both groups. Molecular expressions showed a coherent and biphasic pattern. p-Akt and apoptosis-inducing factor (AIF) were upregulated significantly, with a peak at 8 weeks in the neurectomy group (p <0.01), but cleaved caspase-9 and caspase-3 showed no significant changes in either group. TEM findings showed irreversible and reversible inner-structure disruption and sarcomere discontinuity in the neurectomy and BoNT-A groups, respectively. We demonstrated that denervation induced lasting muscle weight and structural changes of different degrees. Muscle weight reduction by BoNT-A was related to frequency and dose. AIF-mediated caspase-independent apoptosis was significantly different for neurectomy and BoNT-A injection.

AB - Neurectomy and botulinum toxin A (BoNT-A) injection cause denervated muscle atrophy, but questions remain about their clinical utility. We investigated time-series alterations of rat muscle weight, functional deficits, signaling pathways, and microscopic structures, to gain an understanding of the clinical implications. Between 2008 and 2009, the maximal calf circumference of patients for calf reduction either by neurectomy or BoNT-A injections were recorded for study. A rat skeletal muscle model was established through repeated or dose-adjusted BoNT-A injections and neurectomy. The survival, apoptosis pathways, functional deficits, and microscopic structures were investigated using Western blot, sciatic functional index (SFI), and transmission electron microscopy (TEM), respectively. The rat muscle weight ratio of the BoNT-A group had recovered to 89.3 ± 3.8% by week 58, but it never recovered in the neurectomy group. Muscle weight reduction by BoNT-A not only depended on the dose, but additive effects were also obtained through repeated injections. Rat SFI demonstrated rapid recovery in both groups. Molecular expressions showed a coherent and biphasic pattern. p-Akt and apoptosis-inducing factor (AIF) were upregulated significantly, with a peak at 8 weeks in the neurectomy group (p <0.01), but cleaved caspase-9 and caspase-3 showed no significant changes in either group. TEM findings showed irreversible and reversible inner-structure disruption and sarcomere discontinuity in the neurectomy and BoNT-A groups, respectively. We demonstrated that denervation induced lasting muscle weight and structural changes of different degrees. Muscle weight reduction by BoNT-A was related to frequency and dose. AIF-mediated caspase-independent apoptosis was significantly different for neurectomy and BoNT-A injection.

KW - apoptosis

KW - botulinum toxin

KW - denervation

KW - neurectomy

KW - skeletal muscle

UR - http://www.scopus.com/inward/record.url?scp=77955878372&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955878372&partnerID=8YFLogxK

U2 - 10.1089/neu.2010.1320

DO - 10.1089/neu.2010.1320

M3 - Article

VL - 27

SP - 1509

EP - 1516

JO - Journal of Neurotrauma

JF - Journal of Neurotrauma

SN - 0897-7151

IS - 8

ER -