TY - JOUR
T1 - Dexamethasone ameliorates recovery process of neuromuscular junctions after tourniquet-induced ischemia-reperfusion injuries in mouse hindlimb
AU - Tu, Huiyin
AU - Zhang, Dongze
AU - Wadman, Michael C.
AU - Li, Yu Long
N1 - Funding Information:
This study was supported by the Assistant Secretary of Defense for Health Affairs, USA, through the Defense Medical Research and Development Program under Award No. W81XWH-17-1-0037 (to Y-LL).
Funding Information:
This study was supported by the Assistant Secretary of Defense for Health Affairs, USA, through the Defense Medical Research and Development Program under Award No. W81XWH-17-1-0037 (to Y-LL).
Publisher Copyright:
© 2020 The Authors
PY - 2020/9/15
Y1 - 2020/9/15
N2 - 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.
AB - 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.
KW - Cytokine
KW - Dexamethasone
KW - Inflammation
KW - Ischemia-reperfusion injury
KW - Neuromuscular junction
KW - Tourniquet
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U2 - 10.1016/j.ejphar.2020.173364
DO - 10.1016/j.ejphar.2020.173364
M3 - Article
C2 - 32717191
AN - SCOPUS:85088627799
SN - 0014-2999
VL - 883
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
M1 - 173364
ER -