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Anti-inflammatory effect of vagus nerve stimulation in a rat model of inflammatory bowel disease

  • Author Footnotes
    1 The first two authors contributed equally to this work.
    J. Meregnani
    Footnotes
    1 The first two authors contributed equally to this work.
    Affiliations
    Stress et Interactions Neuro-Digestives (SIND, EA3744), Grenoble Institut des Neurosciences (GIN), INSERM U836 UJF-CEA-CHU, Université Joseph Fourier, Site Santé La Tronche, BP170, 38042 Grenoble Cedex 9, France
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  • Author Footnotes
    1 The first two authors contributed equally to this work.
    D. Clarençon
    Footnotes
    1 The first two authors contributed equally to this work.
    Affiliations
    Stress et Interactions Neuro-Digestives (SIND, EA3744), Grenoble Institut des Neurosciences (GIN), INSERM U836 UJF-CEA-CHU, Université Joseph Fourier, Site Santé La Tronche, BP170, 38042 Grenoble Cedex 9, France

    Institut de Recherche Biomédicale des Armées, Antenne de La Tronche, BP87, 38702 La Tronche Cedex, France
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  • M. Vivier
    Affiliations
    Institut de Recherche Biomédicale des Armées, Antenne de La Tronche, BP87, 38702 La Tronche Cedex, France
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  • A. Peinnequin
    Affiliations
    Stress et Interactions Neuro-Digestives (SIND, EA3744), Grenoble Institut des Neurosciences (GIN), INSERM U836 UJF-CEA-CHU, Université Joseph Fourier, Site Santé La Tronche, BP170, 38042 Grenoble Cedex 9, France

    Institut de Recherche Biomédicale des Armées, Antenne de La Tronche, BP87, 38702 La Tronche Cedex, France
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  • C. Mouret
    Affiliations
    Institut de Recherche Biomédicale des Armées, Antenne de La Tronche, BP87, 38702 La Tronche Cedex, France
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  • V. Sinniger
    Affiliations
    Stress et Interactions Neuro-Digestives (SIND, EA3744), Grenoble Institut des Neurosciences (GIN), INSERM U836 UJF-CEA-CHU, Université Joseph Fourier, Site Santé La Tronche, BP170, 38042 Grenoble Cedex 9, France
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  • C. Picq
    Affiliations
    Stress et Interactions Neuro-Digestives (SIND, EA3744), Grenoble Institut des Neurosciences (GIN), INSERM U836 UJF-CEA-CHU, Université Joseph Fourier, Site Santé La Tronche, BP170, 38042 Grenoble Cedex 9, France

    Institut de Recherche Biomédicale des Armées, Antenne de La Tronche, BP87, 38702 La Tronche Cedex, France
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  • A. Job
    Affiliations
    Institut de Recherche Biomédicale des Armées, Antenne de La Tronche, BP87, 38702 La Tronche Cedex, France
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  • F. Canini
    Affiliations
    Stress et Interactions Neuro-Digestives (SIND, EA3744), Grenoble Institut des Neurosciences (GIN), INSERM U836 UJF-CEA-CHU, Université Joseph Fourier, Site Santé La Tronche, BP170, 38042 Grenoble Cedex 9, France

    Institut de Recherche Biomédicale des Armées, Antenne de La Tronche, BP87, 38702 La Tronche Cedex, France
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  • M. Jacquier-Sarlin
    Affiliations
    Stress et Interactions Neuro-Digestives (SIND, EA3744), Grenoble Institut des Neurosciences (GIN), INSERM U836 UJF-CEA-CHU, Université Joseph Fourier, Site Santé La Tronche, BP170, 38042 Grenoble Cedex 9, France
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  • Bruno Bonaz
    Correspondence
    Corresponding author. Stress et Interactions Neuro-Digestives (SIND, EA3744), Grenoble Institut des Neurosciences (GIN), INSERM U836 UJF-CEA-CHU, Université Joseph Fourier, Site Santé La Tronche, BP170, 38042 Grenoble Cedex 09, France. Tel.: +33 4 76 76 55 97; fax: +33 4 76 76 52 97.
    Affiliations
    Stress et Interactions Neuro-Digestives (SIND, EA3744), Grenoble Institut des Neurosciences (GIN), INSERM U836 UJF-CEA-CHU, Université Joseph Fourier, Site Santé La Tronche, BP170, 38042 Grenoble Cedex 9, France

    Clinique Universitaire d'Hépato-Gastroentérologie, CHU de Grenoble, BP217, 38043 Grenoble Cedex 09, France
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  • Author Footnotes
    1 The first two authors contributed equally to this work.
Published:November 12, 2010DOI:https://doi.org/10.1016/j.autneu.2010.10.007

      Abstract

      Vagus nerve stimulation of afferents is used as an adjunctive treatment for drug-resistant epilepsy and depression. In addition, anti-inflammatory properties of vagus nerve stimulation have been reported in various experimental models of inflammation but not in colitis. These effects are thought to be mediated via peripheral release of acetylcholine from the vagus and subsequent activation of macrophages. Our aim was to evaluate in rats the anti-inflammatory effects of chronic vagus nerve stimulation on colonic inflammation. Colitis was induced by intracolonic instillation of trinitrobenzene sulfonic acid. Vagus nerve stimulation (left cervical) was performed in freely moving animals 3 h per day for five consecutive days. Assessment of colonic inflammation was obtained using physiological (e.g. body weight, temperature and locomotor activity) parameters, macroscopical (area of lesions), histological, and biological parameters (e.g. myeloperoxidase activity, cytokine and cytokine-related mRNAs), both at the level of the damaged colon and the colon immediately above. A global multivariate index of colitis was then generated for a better characterization of colonic inflammation. Vagus nerve stimulation reduced the degree of body weight loss and inflammatory markers as observed above the lesion by histological score and myeloperoxidase quantification. This anti-inflammatory effect was also demonstrated by the improvement of the multivariate index of colitis. These data argue for an anti-inflammatory role of vagus nerve stimulation chronically performed in freely moving rats with colitis and provide potential therapeutic applications for patients with inflammatory bowel diseases.

      Keywords

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