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      Cortical stimulation in conscious rats controls joint inflammation

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          Abstract

          The neuronal control of the immune system is fundamental to the development of new therapeutic strategies for inflammatory disorders. Recent studies reported that afferent vagal stimulation attenuates peripheral inflammation by activating specific sympathetic central and peripheral networks, but only few subcortical brain areas were investigated. In the present study, we report that afferent vagal stimulation also activates specific cortical areas, as the parietal and cingulate cortex. Since these cortical structures innervate sympathetic-related areas, we investigate whether electrical stimulation of parietal cortex can attenuate knee joint inflammation in non-anesthetized rats. Our results show that cortical stimulation in rats increased sympathetic activity and improved joint inflammatory parameters, such as local neutrophil infiltration and pro-inflammatory cytokine levels, without causing behavioral disturbance, brain epileptiform activity or neural damage. In addition, we superposed the areas activated by afferent vagal or cortical stimulation to map common central structures to depict a brain immunological homunculus that can allow novel therapeutic approaches against inflammatory joint diseases, such as rheumatoid arthritis.

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          Author and article information

          Journal
          8211617
          6714
          Prog Neuropsychopharmacol Biol Psychiatry
          Prog Neuropsychopharmacol Biol Psychiatry
          Progress in neuro-psychopharmacology & biological psychiatry
          0278-5846
          1878-4216
          4 March 2020
          06 March 2018
          08 June 2018
          28 October 2020
          : 84
          : Pt A
          : 201-213
          Affiliations
          [a ]Department of Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil
          [b ]Translational Research Center for GastroIntestinal Disorders (TARGID), Intestinal Neuroimmune Interactions, University of Leuven, Leuven, Belgium
          [c ]Department of Surgery, Center of Immunology and Inflammation, Rutgers - New Jersey Medical School, Rutgers University, Newark, NJ 07103, USA
          [d ]Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil
          [e ]Department of Neuroscience and Behavioral Sciences, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil
          [f ]Department of Physiological Sciences, Federal University of São Carlos (UFSCAR), São Carlos, SP, Brazil
          [g ]Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil
          Author notes

          Author contributions

          G.S.B., L.U., N.G.C. and A.K. designed the study; G.S.B. and J.A.C. performed the surgical procedures, G.S.B. performed animals experiments and vagus nerve stimulation; G.S.B. performed the ELISA; G.S.B. and V.R.S. performed brain tissue analysis; F.D.V, P.D.P, G.S.B. and N.G.C performed the EEG recordings and cortical electrical stimulation; P.D.P performed the quantitative EEG analysis; G.S.B. prepared the Figures; G.S.B., L.U., N.G.C and A.K. wrote the manuscript; G.J.R., H.C.S., F.Q.C., T.M.C., N.G.C and A.K. provided financial support.

          [* ] Correspondence to: G.S. Bassi, Department of Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil. shimizug@ 123456gmail.com (G.S. Bassi)
          [** ] Correspondence to: L. Ulloa, Department of Surgery, Center of Immunology and Inflammation, Rutgers - New Jersey Medical School, Rutgers University, Newark, NJ 07103, USA. Luis.Ulloa@ 123456Rutgers.edu (L. Ulloa)
          [*** ] Correspondence to: N. Garcia-Cairasco, Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil. ngcairas@ 123456usp.br (N. Garcia-Cairasco)
          [**** ] Correspondence to: A. Kanashiro, Department of Physiological Sciences, Federal University of São Carlos (UFSCAR), São Carlos, SP, Brazil. alex_bioquimica@ 123456yahoo.com.br (A. Kanashiro).
          Article
          PMC7592443 PMC7592443 7592443 nihpa1556102
          10.1016/j.pnpbp.2018.02.013
          7592443
          29522782
          5cf37949-e2b1-47ea-9e82-c2224bf272c3
          History
          Categories
          Article

          Vagus nerve,Neuro-immune interactions,Cortical stimulation,Joint inflammation,Immunological homunculus

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