Cellular changes in denervated tissue during wound healing in a rat model

Abstract

There is increasing evidence that innervation, possibly mediated via neuropeptides, promotes wound healing. This study presents data on the early cellular events during healing in denervated tissue. Free oblique groin flaps were raised on 25 adult Sprague-Dawley rats. Excisional wounds were placed within the flap and in two control sites, the contralateral inguinal region and the thorax. The absence of innervation in the free flap wounds was confirmed 10 days after surgery by indirect immunofluorescence with a pan-neuronal marker. The cellular infiltrate of the wounds was analysed immunohistochemically with a panel of antibodies to rat macrophages and monocytes (ED1), rat B lymphocytes (CD45R) and T lymphocytes (CD2). The immunostained cellular infiltrate was quantified at 2, 4, 7 and 10 days postoperatively. Our results show that denervated wounds have a significantly lower macrophage and T-lymphocyte count at day 4 of wound healing (P < 0.05). Inflammatory cells, particularly macrophages, are known to play an important part in wound healing and their reduced chemotaxis in denervated tissue may be related to the observed delay in wound closure.

CD19, a Response Regulator of B Lymphocytes, Regulates Wound Healing through Hyaluronan-Induced TLR4 Signaling

“…Previous studies have revealed that B cells are present within wound tissue 9 -11 and that B cell count is rapidly increased in the first 4 days after wounding, and thereafter reaches a plateau before falling as the wounds heal. 11 Furthermore, recent assessment of the role of B cells in the immune system has indicated that B cells are more than just the precursors of antibody (Ab)-secreting cells. 12 B cells have essential functions in regulating immune responses, including the production of various cytokines and growth factors, antigen presentation, regulation of T cell activation and differentiation, and regulation of lymphoid organization.…”

Neuropeptídeos na pele

“…5 A capacidade de responder à agressão externa também diminui, pois modelos experimentais demonstram diminuição significativa das contagens de células T e macrófagos em feridas na pele denervada. 6 A comunicação entre ambos os tecidos, cutâneo e nervoso, também parece possuir mecanismos compensatórios. Resultados em animais mostram que, conquanto a pele não seja completamente denervada, apenas uma pequena fração das fibras C cutâneas, de cerca de 30%, já é suficiente para garantir a cicatrização normal das feridas experimentais.…”

Wound Healing in Denervated Rat Groin Skin Flap

“…At the onset of injury, the afferent nerve fibers are stimulated, and they release mediators into the intercellular space which induce changes in the cells of the surrounding tissue [3,14]. It has been proposed that sympathetic efferent nerves also play a significant role in neurogenic inflammation [15].…”

“…The peripheral nervous system regulates wound healing during all its phases, i.e. inflammation, proliferation and remodeling [3,4]. Incomplete regeneration of severed nerves and consequent poor reinnervation of the target tissue may lead to impaired wound healing resulting in chronic ulcers and tissue necrosis [5,6].…”