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Ischemic Tissue Injury in the Dorsal Skinfold Chamber of the Mouse: A Skin Flap Model to Investigate Acute Persistent Ischemia
Published on: November 17, 2014
Topical Neuropeptide Y for Ischemic Skin Wounds
Tais Stangerup1, Lise Mette Rahbek Gjerdrum2,3, Michael Bzorek2
1Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen, Denmark.
Abstract:
Our objective was to investigate the effects of topically applied neuropeptide Y (NPY) on ischemic wounds. Initially, the animal model for ischemic wound healing was validated using 16 male Sprague Dawley albino rats. In the intervention study, an additional 28 rats were divided into three groups: NPY (0.025%), the positive control insulin-like growth factor-I (IGF-I, 0.0025%), and the hydrogel carrier alone (control). The hydrogel was selected due to its capacity to prolong NPY release (p < 0.001), as demonstrated in a Franz diffusion cell. In the animals, an 8 mm full-thickness wound was made in a pedunculated dorsal ischemic skin flap. Wounds were then treated and assessed for 14 days and collected at the end of the experiment for in situ hybridization analysis (RNAscope®) targeting NPY receptor Y2R and for meticulous histologic examination. Wound healing rates, specifically the percentage changes in wound area, did not show an increase with NPY (p = 0.907), but there was an increase with rhIGF-I (p = 0.039) compared to the control. Y2R mRNA was not detected in the wounds or adjacent skin but was identified in the rat brain (used as a positive control). Light microscopic examination revealed trends of increased angiogenesis and enhanced inflammatory cell infiltration with NPY compared to control. An interesting secondary discovery was the presence of melanophages in the wounds. Our findings suggest the potential of NPY to enhance neovascularization under ischemic wound healing conditions, but further optimization of the carrier and dosage is necessary. The mechanism remains elusive but likely involves NPY receptor subtypes other than Y2R.
Insights
Topical neuropeptide Y (NPY) showed potential for enhancing blood vessel growth in ischemic wounds, though it did not accelerate healing rates. Further research is needed to optimize NPY dosage and delivery for wound healing applications.
Area of Science:
- Biomedical research
- Wound healing studies
- Neuropeptide research
Background:
- Ischemic wounds present a significant challenge in healing due to impaired blood supply.
- Neuropeptide Y (NPY) is a peptide with known roles in various physiological processes, including potential roles in tissue repair.
- Understanding the effects of NPY on wound healing is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To investigate the effects of topically applied neuropeptide Y (NPY) on the healing process of ischemic wounds.
- To evaluate the impact of NPY on wound closure rates, neovascularization, and inflammatory responses.
- To explore the expression of NPY receptor Y2R in ischemic wounds.
Main Methods:
- An animal model using Sprague Dawley rats with induced ischemic skin flap wounds was established and validated.
- Wounds were treated with NPY (0.025%), insulin-like growth factor-I (IGF-I, 0.0025%) as a positive control, or a hydrogel carrier alone.
- Wound healing was assessed over 14 days, with analysis including in situ hybridization for Y2R mRNA and histological examination for angiogenesis and inflammation.
Main Results:
- Neuropeptide Y (NPY) did not significantly increase wound healing rates compared to the control group (p = 0.907).
- Recombinant human insulin-like growth factor-I (rhIGF-I) significantly improved wound healing rates (p = 0.039).
- Histological analysis indicated a trend towards increased angiogenesis and inflammatory cell infiltration in NPY-treated wounds, suggesting potential for neovascularization.
Conclusions:
- Topical NPY shows potential for enhancing neovascularization in ischemic wound healing, but did not accelerate overall wound closure in this study.
- The NPY receptor Y2R was not detected in the wound tissue, suggesting other NPY receptor subtypes may be involved in its effects.
- Further optimization of NPY delivery systems and dosage is required to fully elucidate and harness its therapeutic potential in wound healing.
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