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



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.



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.



Dex promotes repair of the NMJ and subsequently restores skeletal muscle contractile function in tourniquet-induced 6-wk IR.
Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
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Zhang
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
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Wang
Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA.
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Pipinos
Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
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Muelleman
Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE, USA.|Department of Cellular & Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA.
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Li
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004594:Electrophysiology; D006614:Hindlimb; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000503:physiopathology; D009469:Neuromuscular Junction / Q000187:drug effects*; D011897:Random Allocation; D020127:Recovery of Function / Q000187:drug effects*; D015427:Reperfusion Injury / Q000503:physiopathology*; D014111:Tourniquets
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone
dexamethasone; endplate potential; ischaemia-reperfusion injury; neuromuscular junction; skeletal muscle; tourniquet