Cutaneous wound healing of chronically stressed mice is improved through catecholamines blockade

Abstract

Stress impairs cutaneous wound healing; however, it is unclear how beta-adrenoceptors participates in alterations induced by stress on skin wound repair. Therefore, the aim of this study was to investigate the effects of propranolol, a non-selective beta-blocker, administration on cutaneous wound healing of chronically stressed mice. Male mice were spun at 115 rpm for 15 min every hour from three days before wounding until euthanasia. Control animals were not submitted to stress. Stressed and control animals were treated with propranolol dissolved in water; controls received only water. Propranolol administration began one day before wounding and was continued daily until euthanasia. A full-thickness excisional lesion was performed. Seven and fourteen days later, animals were killed, and lesions were formalin-fixed and paraffin-embedded. Sections were stained with hematoxylin-eosin and immunostained against F4/80 to quantify macrophages, alpha-smooth muscle actin to quantify the myofibroblast density and proliferating cell nuclear antigen to quantify the cell proliferation. Furthermore, matrix metalloproteinases (MMP)-2 and MMP-9 activity, nitrite and hydroxyproline levels and tumor necrosis factor-alpha (TNF-alpha) expression were measured in wound. Stress and control + propranolol groups presented a delay in wound contraction, re-epithelialization, F4/80-positive macrophages, neutrophils and mast cells infiltration, cellular proliferation, angiogenesis, myofibroblastic differentiation, MMP-2 and MMP-9 activation and TNF-alpha expression, whereas an increase in the nitrite levels. Stress + propranolol group presented results similar to control group. In conclusion, stress impairs cutaneous wound healing in mice through beta1- adrenoceptors and beta2-adrenoceptors activation.

Daily propranolol prevents prolonged mobilization of hematopoietic progenitor cells in a rat model of lung contusion, hemorrhagic shock, and chronic stress

“…This study also demonstrated that CRS following LC and LCHS did worsen healing of injured lung tissue. These findings are supported by Romana-Souza et al (40) who demonstrated that after major burn injuries there was a systemic release of catecholamines that induced a stress state associated with delayed burn wound healing. Similarly, high dose propranolol (25 mg/kg) was shown to block the deleterious effects of circulating catecholamines and improved cutaneous wound healing in burned chronically stressed mice (40).…”

“…These findings are supported by Romana-Souza et al (40) who demonstrated that after major burn injuries there was a systemic release of catecholamines that induced a stress state associated with delayed burn wound healing. Similarly, high dose propranolol (25 mg/kg) was shown to block the deleterious effects of circulating catecholamines and improved cutaneous wound healing in burned chronically stressed mice (40). However, when propranolol dosing was increased to 50 mg/kg in rats Raut et al (41) showed that the beneficial effects of propranolol administration were lost and there was both decreased reepithelialization and collagen density.…”

Mesenchymal stem cells reverse bone marrow dysfunction following injury and stress

“…The role of MSCs on the BM microenvironment has been studied in the setting of co-transplantation with HPCs and in autoimmune diseases marked by chronic inflammation 17–19 . When MSCs are co-transplanted with HPCs at the time of BM transplantation, they enhance the speed of recovery and reduce the incidence of graft-versus host disease (GVHD) 17–18 . MSCs have also been shown to improve blood cell counts in the treatment of refractory cytopenia in patients with systemic lupus erythemaosus 19 .…”

Wound‐associated macrophages control collagen 1α2 transcription during the early stages of skin wound healing

“…The molecular mechanism of the control by macrophages of Col 1 a2 transcription in wounds needs to be further investigated. The direct or indirect production or promotion of TGF-beta could be incriminated for Col 1a2 transcription by competent cells (17). However, other factors that may induce profibrotic mediators by intermediate cell types could also be considered (5,(18)(19)(20).…”