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

Abstract

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 3h of ischaemia following 6weeks 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 insitu. Function of the NMJ was measured insitu 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 3days did not restore the function of the NMJ and improve gastrocnemius muscle contraction in mice with 6-wk IR. Dex treatment for 1week 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.