Dexamethasone ameliorates recovery process of neuromuscular junctions after tourniquet-induced ischemia-reperfusion injuries in mouse hindlimb

Huiyin Tu, Dongze Zhang, Michael C. Wadman, Yu Long Li

Research output: Contribution to journalArticle

Abstract

As a primary tool in first-line treatment of severe extremity hemorrhage, tourniquet and subsequent reperfusion also induce ischemia-reperfusion (IR) injuries including severe dysfunction of the neuromuscular junction (NMJ). Here, we observed the effect of dexamethasone (Dex) on NMJs suffering from IR-cause damage in mouse hindlimb. Unilateral hindlimb of mice was subjected to 3 h of tourniquet application by placing a rubber band, and then releasing the rubber band for reperfusion during different periods of time (1, 2, 4, and 6 weeks). Dex treatment (1 mg/kg/day, i.p.) began on the day of tourniquet-IR induction and lasted for 7 days. During tourniquet-induced IR, NMJs in gastrocnemius muscles showed significant morphological and functional changes. These changes include that motor nerve terminals gradually regenerated, even reaching that seen in sham mice; nicotinic acetylcholine receptor (nAChR) clusters were gradually fragmented with prolongation of reperfusion; and the amplitude of endplate potentials (EPPs) gradually increased, but it did not restore to the sham level at 6 weeks of tourniquet-induced IR. IL-1β and TNFα were over-produced in gastrocnemius muscles at 1 week, gradually decreased to the sham level at 4 weeks, and returned back to a high level at 6 weeks of tourniquet-induced IR. Treatment with Dex mitigated fragmentation of nAChR clusters, increased the amplitude of EPPs, and decreased levels of TNFα and IL-1β during the first two weeks of tourniquet-induced IR. The present study suggests that anti-inflammation is a potentially important strategy for promoting the morphological and functional recovery processes of NMJs after tourniquet-induced IR injuries.

Original languageEnglish (US)
Article number173364
JournalEuropean Journal of Pharmacology
Volume883
DOIs
StatePublished - Sep 15 2020

Keywords

  • Cytokine
  • Dexamethasone
  • Inflammation
  • Ischemia-reperfusion injury
  • Neuromuscular junction
  • Tourniquet

ASJC Scopus subject areas

  • Pharmacology

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