Age-associated differences in macrophage response in a vaginal wound healing rat model

Introduction and hypothesis: Surgical treatment of pelvic organ prolapse often includes the use of patients’ vaginal connective tissue. Wound healing appears to play an important part in the success of such procedures. The aim of this study was to describe the effect of age on inflammatory processes, specifically macrophage response, involved in vaginal wound healing. Methods: Twenty-five young (12 weeks old) and 25 old (12 months old) virgin female Fischer rats underwent a standardized 9-mm posterior midline vaginal incision. Tissue samples were taken for histological analysis on days 1, 3, 7, 14 and 30 post-injury. Parameters evaluated included wound area, macrophage number and expression of inflammatory markers including tumor necrosis factor alpha (TNFa), inducible nitric oxide synthase (iNOS), CCR7/CD197, arginase I and CD163/M130. Results: Microscopic examination of the vaginal wounds over time demonstrated a clear difference between young and old rats in spontaneous healing capacity. The average wound area in young rats 1 day after injury was significantly smaller than in old rats (16.5 ± 1.7 vs. 23.8 ± 1.5 mm², P < 0.05). At 3 days post-injury, wounds were closed in young rats but still open in old rats (wound area: 13.5 ± 1.5 mm²). Old rats demonstrated a more excessive and sustained macrophage response compared with young rats. They also demonstrated a disordered pattern of macrophage expression over time, with a prolonged expression of TNFa and iNOS in the tissue and a disordered M2 macrophage response. Conclusion: Excessive and prolonged macrophage response in older rats may contribute to poor wound healing in the vagina.