Dexamethasone Improves Neuromuscular Junction Recovery From Ischemia‐Reperfusion Injury Induced by Tourniquet Application in Mouse Hindlimb

Abstract

Tourniquet‐induced ischemia‐reperfusion (IR) injuries impede long‐term recovery of skeletal muscle contraction. The neuromuscular junction (NMJ) is an important factor to influence skeletal muscle contractile function. Here, we observed the effect of dexamethasone (Dex) on morphological and functional recovery of the NMJ from tourniquet‐induced IR injuries in mouse hindlimb.Unilateral hindlimb of C57/BL6 mice were subjected to 3 hours of ischemia by placing a rubber band and followed different periods of reperfusion (1 week, 2 weeks, 4 weeks, and 6 weeks). Dex treatment (1 mg/kg/day, i.p.) began on the day of IR induction and lasted for 7 days. After 3 hours of ischemia and different periods of reperfusion, NMJs in the gastrocnemius muscle showed significantly the morphological and functional damage. In the gastrocnemius muscle, TNFα and IL‐1β (two inflammatory cytokines) were increased after 1, 2 and 6 weeks of tourniquet‐induced IR. Treatment with Dex inhibited the elevation of TNFα and IL‐1β, mitigated fragmentation of nicotinic acetylcholine receptor (nAChR) clusters, promoted re‐innervation of nAChR clusters, and increased nerve‐stimulated end plate potentials (EPPs).The data suggested that tourniquet‐related IR induced serious skeletal muscle inflammation for a long period. Dex treatment for 1 week inhibits IR‐caused inflammation in the early period of IR, and improves the morphological and functional recovery of the NMJ from tourniquet‐induced IR injuries.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.