Ribavirin reduces clinical signs and pathological changes of experimental autoimmune encephalomyelitis in Dark Agouti rats
Autor: | Stanislava Stosic-Grujicic, Vjera Pejanovic, Ljubica Medić-Mijačević, Ljubisav Rakic, Sanja Subasic, Mirjana Stojiljkovic, Irena Milicevic, Sanja Pekovic, Marija Mostarica-Stojkovic |
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Rok vydání: | 2003 |
Předmět: |
Encephalomyelitis
Autoimmune Experimental medicine.medical_treatment Peripheral blood mononuclear cell 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Adjuvants Immunologic Ribavirin medicine Animals 030304 developmental biology 0303 health sciences Nucleoside analogue Microglia business.industry Macrophages Multiple sclerosis Experimental autoimmune encephalomyelitis Rats Inbred Strains Immunosuppression medicine.disease Rats 3. Good health Disease Models Animal Neuroprotective Agents medicine.anatomical_structure Spinal Cord chemistry Immunology Female Disease Susceptibility business Adjuvant Immunosuppressive Agents 030217 neurology & neurosurgery Demyelinating Diseases medicine.drug |
Zdroj: | Journal of Neuroscience Research |
ISSN: | 1097-4547 0360-4012 |
DOI: | 10.1002/jnr.10552 |
Popis: | The effect of ribavirin on development of experimental autoimmune encephalomyelitis (EAE) was investigated. The disease was induced in genetically susceptible Dark Agouti rats with syngeneic spinal cord homogenate in complete Freund's adjuvant (SCH-CFA). Depending on the amount of mycobacteria in CFA, the animals developed either moderate or severe EAE. Ribavirin (1-beta-Dribofuranosyl-1,2,4-triazole-3-carboxamide) was applied i.p. at a daily dosage of 30 mg/kg in two treatment protocols: from the start of immunization (preventive treatment) or from the onset of the first EAE signs after the induction (therapeutic treatment). Signs of EAE began between 7 and 9 days after induction and peaked at days 11-13. In moderate EAE (mean maximal severity score 3.33 +/- 0.21), the recovery was completed by days 23-26, whereas, in severe EAE (mean maximal severity score 4.5 +/- 0.23), obvious recovery was not detected. Preventive ribavirin treatment significantly decreased clinical signs after both moderate (score 1.75 +/- 0.25, P < 0.05) and severe (score 3.62 +/- 0.31, P < 0.015) immunization. Also, disease manifestations were reduced by therapeutic treatment of ribavirin (mean maximal severity score 2.5 +/- 0.2 vs. 3.33 +/- 0.21 in controls, P < 0.005) but less so in comparison with preventive treatment. Analysis of the effects of ribavirin on histopathologic changes in the spinal cord tissue revealed a reduction of mononuclear cell infiltrates, composed of T cells and macrophages/microglia, and the absence of demyelination, which were pronounced in control EAE animals. Beneficial effects of preventive and therapeutic treatment with ribavirin on development of EAE suggest this nucleoside analogue as a useful candidate for therapy in multiple sclerosis. (C) 2003 Wiley-Liss, Inc. null |
Databáze: | OpenAIRE |
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