Ryan M. Corrick, Huiyin Tu, Dongze Zhang, Aaron N. Barksdale, Robert L. Muelleman, Michael C. Wadman, Yu-Long Li
Abstract
Extremity injuries with hemorrhage have been a significant cause of death in civilian medicine and on the battlefield. The use of a tourniquet as an intervention is necessary for treatment to an injured limb; however, the tourniquet and subsequent release results in serious acute ischemia-reperfusion (IR) injury in the skeletal muscle and neuromuscular junction (NMJ). Much evidence demonstrates that inflammation is an important factor to cause acute IR injury. To find effective therapeutic interventions for tourniquet-induced acute IR injuries, our current study investigated effect of dexamethasone, an anti-inflammatory drug, on tourniquet-induced acute IR injury in mouse hindlimb. In C57/BL6 mice, a tourniquet was placed on unilateral hindlimb (left hindlimb) at the hip joint for 3 h, and then released for 24 h to induce IR. Three hours of tourniquet and 24 h of release (24-h IR) caused gastrocnemius muscle injuries including rupture of the muscle sarcolemma and necrosis (42.8 ± 2.3% for infarct size of the gastrocnemius muscle). In the NMJ, motor nerve terminals disappeared, and endplate potentials were undetectable in 24-h IR mice. There was no gastrocnemius muscle contraction in 24-h IR mice. Western blot data showed that inflammatory cytokines (TNFα and IL-1β) were increased in the gastrocnemius muscle after 24-h IR. Treatment with dexamethasone at the beginning of reperfusion (1 mg/kg, i.p.) significantly inhibited expression of TNFα and IL-1β, reduced rupture of the muscle sarcolemma and infarct size (24.8 ± 2.0%), and improved direct muscle stimulation-induced gastrocnemius muscle contraction in 24-h IR mice. However, this anti-inflammatory drug did not improve NMJ morphology and function, and sciatic nerve-stimulated skeletal muscle contraction in 24-h IR mice. The data suggest that one-time treatment with dexamethasone at the beginning of reperfusion only reduced structural and functional impairments of the skeletal muscle but not the NMJ through inhibiting inflammatory cytokines.
Pharmacology, Toxicology and Pharmaceutical Science
2
8%
Biochemistry, Genetics and Molecular Biology
2
8%
Sports and Recreations
2
8%
Other
1
4%
Unknown
6
25%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 November 2021.
All research outputs
#17,789,339
of 26,052,823 outputs
Outputs from Frontiers in Physiology
#7,713
of 15,756 outputs
Outputs of similar age
#228,039
of 351,336 outputs
Outputs of similar age from Frontiers in Physiology
#220
of 420 outputs
Altmetric has tracked 26,052,823 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 15,756 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.3. This one is in the 47th percentile – i.e., 47% of its peers scored the same or lower than it.
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We're also able to compare this research output to 420 others from the same source and published within six weeks on either side of this one. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.
