Dexamethasone Improves Wound Healing by Decreased Inflammation and Increased Vasculogenesis in Mouse Skin Frostbite Model

Huiyin Tu, Dongze Zhang, Aaron N. Barksdale, Michael C. Wadman, Robert L. Muelleman, Yu Long Li

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Frostbite is thought to result from initial vasoconstriction, ischemia, intracellular ice crystal formation, and inflammation caused by reperfusion injury. Corticosteroids have demonstrated beneficial anti-inflammatory effects in the treatment of other ischemia/reperfusion clinical conditions. The objective of this study was to determine the effect of dexamethasone (dex) on wound healing, inflammatory response, and vasculogenesis in a mouse skin frostbite model. Methods: Treatment and control groups of C57/BL6 mice were subjected to frostbite using a previously described model. Treatment with intraperitoneal dex (1 mg·kg-1·d-1) began on the day of frostbite induction and lasted for 7 d. Over 4 wk, we compared wound diameter; morphology by visual inspection, hematoxylin–eosin staining, and Masson's trichrome staining; density of inflammatory cytokines IL-1β and TNFα using Western blot analysis; and formation of microvasculature using immunofluorescence staining. Data were analyzed using 1-way or 1-way repeated-measures analysis of variance. Results: After frostbite injury, morphological images demonstrated epidermal necrosis and loss in the frostbitten skin as well as infiltration of inflammation-related leukocytes. Increased production of inflammatory cytokines and disappearance of the microvasculature also occurred in the frostbitten skin. In comparison to the control group, treatment with dex promoted wound healing as demonstrated by decreased wound diameter; decreased levels of inflammatory cytokines, and accelerated formation of mature microvasculature. Conclusions: In this animal model, dex improved wound healing in frostbitten skin and demonstrated both anti-inflammatory effects and stimulation of vasculogenesis. This study suggests that the use of potent anti-inflammatory agents may be an effective strategy for mitigating frostbite injury.

Original languageEnglish (US)
Pages (from-to)407-417
Number of pages11
JournalWilderness and Environmental Medicine
Volume31
Issue number4
DOIs
StatePublished - Dec 2020

Keywords

  • animal
  • collagen
  • cytokine
  • ischemia
  • microvasculature
  • reperfusion

ASJC Scopus subject areas

  • Emergency Medicine
  • Public Health, Environmental and Occupational Health

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