RESUMEN
The skin is a natural barrier between the interior milieu of the organism and its environment. This barrier has multiple physiological functions and may be affected by an array of pathologies including wounds and burns. The present study aims to determine the effect of the nervous system on wound healing. Specifically, this study tested the effect of denervation by chemical ablation on the burn wound healing process using guanethidine for denervation of the sympathetic postganglionic neurons and resiniferatoxin for denervation of the sensory capsaicin-sensitive fibres. Animals were divided into 8 different groups: (1) control group, (2) sensory denervated and burned, (3) sensory denervated non-burned, (4) sympathetic denervated and burned, (5) sympathetic denervated non-burned, (6) vehicle sensory burned, (7) vehicle sympathetic burned, (8) non-denervated burned. We measured different morphologic and biochemical parameters such as wound surface area, histological alterations and mast cells. In addition, NGF, IL-1ß, IL-6 and IL-8 levels were determined using the ELISA technique. The gross observations, the histological data including mast cell modulation, as well as the molecular data, speak in favour of a significant delay in burn wound healing caused by sensory denervation. On the other hand, results support the positive role of sympathetic denervation in speeding up the healing process. The dual effect of the nervous system on burn wound healing is being documented in an animal model for the first time.
La peau est une barrière naturelle entre le milieu intérieur et son environnement. Elle a des fonctions physiologiques multiples et peut être atteinte par de nombreuses pathologies parmi lesquelles plaies et brûlures. Cette étude a pour but d'évaluer les effets du système nerveux sur la cicatrisation et plus particulièrement ceux de la dénervation chimique par guanéthidine des neurones sympathiques post ganglionnaires ainsi que celle des fibres sensitives à capsaïcine par résiniferatoxine. Des animaux ont été répartis en 8 groupes : (1) contrôle, (2) dénervation sensitive + brûlure, (3) dénervation sensitive sans brûlure, (4) dénervation sympathique + brûlure, (5) dénervation sympathique sans brûlure, (6) solvant de résiniferatoxine + brûlure, (7) solvant de guanéthidine + brûlure, (8) pas de dénervation + brûlure. Nous avons mesuré plusieurs paramètres morphologiques et biochimiques parmi lesquels la surface brûlées, les anomalies histologiques et la fonction mastocytaire. NGF, IL1b, IL6 et IL8 ont été mesurés par méthode ELISA. L'observation clinique, les données histologiques dont la modulation mastocytaire ainsi que les données moléculaires orientent vers un ralentissement de la cicatrisation après dénervation sensitive alors que la dénervation sympathique l'accélère. C'est la première fois que ces effets opposés des dénervations sélective est observée chez l'animal.
RESUMEN
Integrins can modulate the infiltration of inflammatory cells and the secretion of various inflammatory mediators, essential players in the pathogenesis of colitis. This study explores the role of beta2 and beta3 integrin signaling and their possible role in experimental colitis. A total of 160 adult male Sprague-Dawly rats were divided into 4 equal groups: methylcellulose, bacteria, iodoacetamide and iodoacetamide plus bacteria. Clinical symptoms and signs of colitis were checked daily and colonic tissues were biopsied on days 3, 14, 28, and 56 post induction. Histological studies along with histochemical analysis and polymerase chain reaction of beta2, beta3 and alphavbeta3 were performed according to standard procedures. The symptoms and signs were consistent with previously reported data on active colitis. The highest expression of beta3 integrin was in the combined treatment mostly on platelets, endothelial and inflammatory cells. In the same group, the expression of alphavbeta3 integrin complex reached the highest score after 56 days in all colonic layers. Beta2 integrin expression showed a 3-4-fold increase in the combined treatment group at all time points and kept increasing till day 56. It was mostly expressed in the mucosa and submucosa. In addition, the expression of both αvβ3 and αiiβ3 integrins was also elevated 2- to 10-fold, respectively, in the same colitis groups throughout the duration of the experiment. In conclusion, the combined treatment of IA and Enteropathogenic E. coli led to a significant upregulation of all the tested integrins throughout the experimental duration. Such upregulation of integrins could have contributed to the increase and chronicity of inflammation.