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Dexamethasone Promotes the Long‐Term Functional Recovery of Neuromuscular Junction after Ischemia/Reperfusion Injury Induced by Tourniquet in Mouse Hindlimb
Author(s) -
Zhang Dongze,
Wang Dong,
Muelleman Robert L.,
Li YuLong
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1245.1
Subject(s) - hindlimb , medicine , tourniquet , skeletal muscle , ischemia , sciatic nerve , anesthesia , neuromuscular junction , gastrocnemius muscle , reperfusion injury , dexamethasone , endocrinology , biology , neuroscience
Tourniquet application is an effective means of arresting life‐threatening limb hemorrhage in pre‐hospital setting. However, tourniquet‐induced ischemia and subsequent reperfusion cause serious ischemia‐reperfusion (IR) injury for the neuromuscular junction and limb. Although accumulating evidence has uncovered protective effects of anti‐inflammation and anti‐oxidation on acute IR injury in skeletal muscles, it is unclear whether these therapies improve long‐term functions of the neuromuscular junction and skeletal muscle. Our current study investigated if Dexamethasone (Dex) promotes repair of the neuromuscular junction and restore the skeletal muscle contractile function in tourniquet‐induced hindlimb IR. Unilateral hindlimb of C57/BL6 mice was subjected to 3‐hours of ischemia following 6‐weeks of reperfusion (6‐wk‐IR) via placement and release of a tourniquet at the hip joint. To test the protective effect of Dex, Dex treatment (1mg/kg/day, i.p.) began on the day of IR induction and lasted for varied periods including 1 day, 3 days, 1 week, 2 weeks, 4 weeks and 6 weeks. On the day of the terminal experiments, gastrocnemius muscle contraction was detected under sciatic nerve stimulation (10 V, 50 Hz, 5 sec) in situ. Function of the neuromuscular junction was measured using electrophysiological recording of endplate potentials (EPP) in situ. Western blot was used to detect the protein expression of nAchR α1 and nAchR β1 in gastrocnemius muscles. The amplitude of EPP was lower in mice with 6‐wk‐IR than that in sham mice. Additionally, sciatic nerve‐stimulated gastrocnemius muscle contraction in mice with 6‐wk‐IR was 60% of normal skeletal muscle contraction recorded in age‐matched sham mice. Dex treatment for 1 or 3 days did not significantly increase amplitude of EPP and improve sciatic nerve‐stimulated gastrocnemius muscle contraction in tourniquet‐induced 6‐wk‐IR. Dex treatment for 1‐week exerted a maximum effect on increasing amplitude of EPP and improving skeletal muscle contraction, which were gradually becoming less, and even deleterious, with prolonged Dex treatment. Furthermore, there are no significant differences in protein expression of nAchR α1 and nAchR β1 in gastrocnemius muscle between groups. These results suggest that 1‐week is an optimum duration for application of Dex to promote repair of neuromuscular junction and improve long‐term recovery of IR‐induced skeletal muscle contraction. Simultaneously, these results also indicate the toxic effect of Dex on the neuromuscular junction and skeletal muscle after prolonged treatment of Dex.