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Artesunate Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting Leukocyte Migration to the Central Nervous System

Byline: Rodolfo Thome, Ana Carolina Carvalho, Thiago Alves da Costa, Larissa Lumi Watanabe Ishikawa, Thais Fernanda de Campos Fraga-Silva, Alexandrina Sartori, Alexandre Leite Rodrigues Oliveira, Liana Verinaud Keywords: Artesunate; Cellular migration; Experimental autoimmune encephalomyelitis; Neur... Full description

Journal Title: CNS Neuroscience & Therapeutics August 2016, Vol.22(8), pp.707-714
Main Author: Thomé, Rodolfo
Other Authors: Carvalho, Ana Carolina , Alves Da Costa, Thiago , Ishikawa, Larissa Lumi Watanabe , Fraga‐Silva, Thais Fernanda De Campos , Sartori, Alexandrina , Oliveira, Alexandre Leite Rodrigues , Verinaud, Liana
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ID: ISSN: 1755-5930 ; E-ISSN: 1755-5949 ; DOI: 10.1111/cns.12561
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recordid: wj10.1111/cns.12561
title: Artesunate Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting Leukocyte Migration to the Central Nervous System
format: Article
creator:
  • Thomé, Rodolfo
  • Carvalho, Ana Carolina
  • Alves Da Costa, Thiago
  • Ishikawa, Larissa Lumi Watanabe
  • Fraga‐Silva, Thais Fernanda De Campos
  • Sartori, Alexandrina
  • Oliveira, Alexandre Leite Rodrigues
  • Verinaud, Liana
subjects:
  • Artesunate
  • Cellular Migration
  • Experimental Autoimmune Encephalomyelitis
  • Neuroinflammation
ispartof: CNS Neuroscience & Therapeutics, August 2016, Vol.22(8), pp.707-714
description: Byline: Rodolfo Thome, Ana Carolina Carvalho, Thiago Alves da Costa, Larissa Lumi Watanabe Ishikawa, Thais Fernanda de Campos Fraga-Silva, Alexandrina Sartori, Alexandre Leite Rodrigues Oliveira, Liana Verinaud Keywords: Artesunate; Cellular migration; Experimental autoimmune encephalomyelitis; Neuroinflammation Summary Background and Aims Experimental autoimmune encephalomyelitis (EAE) is T-cell-dependent disease of the central nervous system (CNS) of mice. This model resembles multiple sclerosis (MS) in many aspects. Therapies that focus in the modulation of the immune response and cellular infiltration in the CNS present best effects in the clinics. Artesunate (Art) is a semi-synthetic sesquiterpene derivative from artemisinin and has been shown to reduce the clinical signs of autoimmune disease models through mechanisms not yet understood. In this study, we aimed to evaluate whether administration of Art would ameliorate EAE. Methods and Results C57BL6 mice were immunized with MOG.sub.35-55 peptide to induce EAE. At the same time, Art treatment started (3 mg/kg/day via i.p.) for five consecutive days. We found that Art treatment reduced the clinical signs of EAE and that correlated with a reduced infiltration of cells in the CNS. Disease amelioration did not correlate with immunomodulation as recall responses, leukocyte subpopulations, and gene expression analysis were similar among treated and untreated mice. Ultimately, further analysis provided data indicating that a possible mechanism of action for Art is dependent on the cellular migration to the CNS. Conclusions Artesunate reduces the severity of EAE by inhibiting migration of pathogenic T cells to the CNS.
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identifier: ISSN: 1755-5930 ; E-ISSN: 1755-5949 ; DOI: 10.1111/cns.12561
fulltext: fulltext
issn:
  • 1755-5930
  • 17555930
  • 1755-5949
  • 17555949
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titleArtesunate Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting Leukocyte Migration to the Central Nervous System
creatorThomé, Rodolfo ; Carvalho, Ana Carolina ; Alves Da Costa, Thiago ; Ishikawa, Larissa Lumi Watanabe ; Fraga‐Silva, Thais Fernanda De Campos ; Sartori, Alexandrina ; Oliveira, Alexandre Leite Rodrigues ; Verinaud, Liana
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subjectArtesunate ; Cellular Migration ; Experimental Autoimmune Encephalomyelitis ; Neuroinflammation
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descriptionByline: Rodolfo Thome, Ana Carolina Carvalho, Thiago Alves da Costa, Larissa Lumi Watanabe Ishikawa, Thais Fernanda de Campos Fraga-Silva, Alexandrina Sartori, Alexandre Leite Rodrigues Oliveira, Liana Verinaud Keywords: Artesunate; Cellular migration; Experimental autoimmune encephalomyelitis; Neuroinflammation Summary Background and Aims Experimental autoimmune encephalomyelitis (EAE) is T-cell-dependent disease of the central nervous system (CNS) of mice. This model resembles multiple sclerosis (MS) in many aspects. Therapies that focus in the modulation of the immune response and cellular infiltration in the CNS present best effects in the clinics. Artesunate (Art) is a semi-synthetic sesquiterpene derivative from artemisinin and has been shown to reduce the clinical signs of autoimmune disease models through mechanisms not yet understood. In this study, we aimed to evaluate whether administration of Art would ameliorate EAE. Methods and Results C57BL6 mice were immunized with MOG.sub.35-55 peptide to induce EAE. At the same time, Art treatment started (3 mg/kg/day via i.p.) for five consecutive days. We found that Art treatment reduced the clinical signs of EAE and that correlated with a reduced infiltration of cells in the CNS. Disease amelioration did not correlate with immunomodulation as recall responses, leukocyte subpopulations, and gene expression analysis were similar among treated and untreated mice. Ultimately, further analysis provided data indicating that a possible mechanism of action for Art is dependent on the cellular migration to the CNS. Conclusions Artesunate reduces the severity of EAE by inhibiting migration of pathogenic T cells to the CNS.
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