7 Citations (Scopus)

Abstract

Aim: Tourniquet-induced ischaemia and subsequent reperfusion cause serious ischaemia–reperfusion (IR) injury in the neuromuscular junction (NMJ) and skeletal muscle. Here, we investigated whether dexamethasone (Dex) promotes long-term functional recovery of the NMJ and skeletal muscle in tourniquet-induced hindlimb IR. Methods: Unilateral hindlimb of C57/BL6 mice was subjected to 3 h of ischaemia following 6 weeks of reperfusion (6-wk IR). Dex treatment began on the day of IR induction and lasted for different periods. Sciatic nerve-stimulated gastrocnemius muscle contraction was detected in situ. Function of the NMJ was measured in situ using electrophysiological recording of the miniature endplate potential (mEPP) and endplate potential (EPP). Western blot was used to detect protein expression of nicotinic acetylcholine receptors (nAChRs) in gastrocnemius muscles. Results: Gastrocnemius muscle contraction in mice with 6-wk IR was about 60% of normal skeletal muscle contraction recorded in age-matched sham mice. The amplitude of the mEPP and EPP was lower in mice with 6-wk IR, compared to sham mice. Dex treatment for 1 or 3 days did not restore the function of the NMJ and improve gastrocnemius muscle contraction in mice with 6-wk IR. Dex treatment for 1 week exerted a maximum effect on improving the function of the NMJ and skeletal muscle, with the effect of Dex gradually lessening with prolonged Dex treatment. There are no significant differences in protein expression of nAChR-α1 and nAChR-β1 subunits in the gastrocnemius muscle among all groups. Conclusion: Dex promotes repair of the NMJ and subsequently restores skeletal muscle contractile function in tourniquet-induced 6-wk IR.

Original languageEnglish (US)
Pages (from-to)453-464
Number of pages12
JournalActa Physiologica
Volume219
Issue number2
DOIs
StatePublished - Feb 1 2017

Fingerprint

Tourniquets
Neuromuscular Junction
Dexamethasone
Skeletal Muscle
Muscle Contraction
Hindlimb
Reperfusion
Ischemia
Nicotinic Receptors
Sciatic Nerve
Proteins
Western Blotting

Keywords

  • dexamethasone
  • endplate potential
  • ischaemia–reperfusion injury
  • neuromuscular junction
  • skeletal muscle
  • tourniquet

ASJC Scopus subject areas

  • Physiology

Cite this

@article{5665318def404d9c9312bb63a613fe75,
title = "Dexamethasone promotes long-term functional recovery of neuromuscular junction in a murine model of tourniquet-induced ischaemia–reperfusion",
abstract = "Aim: Tourniquet-induced ischaemia and subsequent reperfusion cause serious ischaemia–reperfusion (IR) injury in the neuromuscular junction (NMJ) and skeletal muscle. Here, we investigated whether dexamethasone (Dex) promotes long-term functional recovery of the NMJ and skeletal muscle in tourniquet-induced hindlimb IR. Methods: Unilateral hindlimb of C57/BL6 mice was subjected to 3 h of ischaemia following 6 weeks of reperfusion (6-wk IR). Dex treatment began on the day of IR induction and lasted for different periods. Sciatic nerve-stimulated gastrocnemius muscle contraction was detected in situ. Function of the NMJ was measured in situ using electrophysiological recording of the miniature endplate potential (mEPP) and endplate potential (EPP). Western blot was used to detect protein expression of nicotinic acetylcholine receptors (nAChRs) in gastrocnemius muscles. Results: Gastrocnemius muscle contraction in mice with 6-wk IR was about 60{\%} of normal skeletal muscle contraction recorded in age-matched sham mice. The amplitude of the mEPP and EPP was lower in mice with 6-wk IR, compared to sham mice. Dex treatment for 1 or 3 days did not restore the function of the NMJ and improve gastrocnemius muscle contraction in mice with 6-wk IR. Dex treatment for 1 week exerted a maximum effect on improving the function of the NMJ and skeletal muscle, with the effect of Dex gradually lessening with prolonged Dex treatment. There are no significant differences in protein expression of nAChR-α1 and nAChR-β1 subunits in the gastrocnemius muscle among all groups. Conclusion: Dex promotes repair of the NMJ and subsequently restores skeletal muscle contractile function in tourniquet-induced 6-wk IR.",
keywords = "dexamethasone, endplate potential, ischaemia–reperfusion injury, neuromuscular junction, skeletal muscle, tourniquet",
author = "D. Zhang and Dong Wang and Pipinos, {Iraklis I} and Muelleman, {Robert Leo} and Yulong Li",
year = "2017",
month = "2",
day = "1",
doi = "10.1111/apha.12737",
language = "English (US)",
volume = "219",
pages = "453--464",
journal = "Acta Physiologica",
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number = "2",

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TY - JOUR

T1 - Dexamethasone promotes long-term functional recovery of neuromuscular junction in a murine model of tourniquet-induced ischaemia–reperfusion

AU - Zhang, D.

AU - Wang, Dong

AU - Pipinos, Iraklis I

AU - Muelleman, Robert Leo

AU - Li, Yulong

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Aim: Tourniquet-induced ischaemia and subsequent reperfusion cause serious ischaemia–reperfusion (IR) injury in the neuromuscular junction (NMJ) and skeletal muscle. Here, we investigated whether dexamethasone (Dex) promotes long-term functional recovery of the NMJ and skeletal muscle in tourniquet-induced hindlimb IR. Methods: Unilateral hindlimb of C57/BL6 mice was subjected to 3 h of ischaemia following 6 weeks of reperfusion (6-wk IR). Dex treatment began on the day of IR induction and lasted for different periods. Sciatic nerve-stimulated gastrocnemius muscle contraction was detected in situ. Function of the NMJ was measured in situ using electrophysiological recording of the miniature endplate potential (mEPP) and endplate potential (EPP). Western blot was used to detect protein expression of nicotinic acetylcholine receptors (nAChRs) in gastrocnemius muscles. Results: Gastrocnemius muscle contraction in mice with 6-wk IR was about 60% of normal skeletal muscle contraction recorded in age-matched sham mice. The amplitude of the mEPP and EPP was lower in mice with 6-wk IR, compared to sham mice. Dex treatment for 1 or 3 days did not restore the function of the NMJ and improve gastrocnemius muscle contraction in mice with 6-wk IR. Dex treatment for 1 week exerted a maximum effect on improving the function of the NMJ and skeletal muscle, with the effect of Dex gradually lessening with prolonged Dex treatment. There are no significant differences in protein expression of nAChR-α1 and nAChR-β1 subunits in the gastrocnemius muscle among all groups. Conclusion: Dex promotes repair of the NMJ and subsequently restores skeletal muscle contractile function in tourniquet-induced 6-wk IR.

AB - Aim: Tourniquet-induced ischaemia and subsequent reperfusion cause serious ischaemia–reperfusion (IR) injury in the neuromuscular junction (NMJ) and skeletal muscle. Here, we investigated whether dexamethasone (Dex) promotes long-term functional recovery of the NMJ and skeletal muscle in tourniquet-induced hindlimb IR. Methods: Unilateral hindlimb of C57/BL6 mice was subjected to 3 h of ischaemia following 6 weeks of reperfusion (6-wk IR). Dex treatment began on the day of IR induction and lasted for different periods. Sciatic nerve-stimulated gastrocnemius muscle contraction was detected in situ. Function of the NMJ was measured in situ using electrophysiological recording of the miniature endplate potential (mEPP) and endplate potential (EPP). Western blot was used to detect protein expression of nicotinic acetylcholine receptors (nAChRs) in gastrocnemius muscles. Results: Gastrocnemius muscle contraction in mice with 6-wk IR was about 60% of normal skeletal muscle contraction recorded in age-matched sham mice. The amplitude of the mEPP and EPP was lower in mice with 6-wk IR, compared to sham mice. Dex treatment for 1 or 3 days did not restore the function of the NMJ and improve gastrocnemius muscle contraction in mice with 6-wk IR. Dex treatment for 1 week exerted a maximum effect on improving the function of the NMJ and skeletal muscle, with the effect of Dex gradually lessening with prolonged Dex treatment. There are no significant differences in protein expression of nAChR-α1 and nAChR-β1 subunits in the gastrocnemius muscle among all groups. Conclusion: Dex promotes repair of the NMJ and subsequently restores skeletal muscle contractile function in tourniquet-induced 6-wk IR.

KW - dexamethasone

KW - endplate potential

KW - ischaemia–reperfusion injury

KW - neuromuscular junction

KW - skeletal muscle

KW - tourniquet

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U2 - 10.1111/apha.12737

DO - 10.1111/apha.12737

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