Erythropoietin reduces experimental autoimmune encephalomyelitis severity via neuroprotective mechanisms
| العنوان: | Erythropoietin reduces experimental autoimmune encephalomyelitis severity via neuroprotective mechanisms |
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| المؤلفون: | M. Bednar, Omolara O. Ogunshola, M. Moransard, Max Gassmann, K. Frei |
| المساهمون: | University of Zurich, Ogunshola, O O |
| المصدر: | Journal of Neuroinflammation Journal of Neuroinflammation, Vol 14, Iss 1, Pp 1-13 (2017) |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Central Nervous System, purl.org/pe-repo/ocde/ford#3.02.25 [https], Cytokines/genetics/metabolism, 2804 Cellular and Molecular Neuroscience, Neurons/metabolism/pathology, lcsh:RC346-429, Monocytes, Myelin, Mice, 0302 clinical medicine, Erythropoietin/genetics/metabolism, Central Nervous System/metabolism/pathology, Lymphocytes, 10064 Neuroscience Center Zurich, Neurons, Experimental autoimmune encephalomyelitis, biology, Monocytes/pathology, EAE, General Neuroscience, 2800 General Neuroscience, Proto-Oncogene Proteins c-sis, 10081 Institute of Veterinary Physiology, Spleen/pathology, Neuroprotection, purl.org/pe-repo/ocde/ford#3.01.03 [https], Gene Expression Regulation/drug effects/genetics, Neuroprotection/drug effects/genetics/physiology, medicine.anatomical_structure, Neurology, Encephalomyelitis, Autoimmune, Experimental/chemically induced/pathology/therapy, Cytokines, Lymphocytes/pathology, Female, medicine.drug, Encephalomyelitis, Autoimmune, Experimental, Macrophages/metabolism/pathology, Immunology, Central nervous system, Mice, Transgenic, Myelin oligodendrocyte glycoprotein, Multiple sclerosis, Immunomodulation, 03 medical and health sciences, Cellular and Molecular Neuroscience, Immune system, medicine, Myelin-Oligodendrocyte Glycoprotein/immunology/toxicity, Animals, Humans, Erythropoietin, lcsh:Neurology. Diseases of the nervous system, 2403 Immunology, Proto-Oncogene Proteins c-sis/genetics/metabolism, business.industry, Macrophages, Research, purl.org/pe-repo/ocde/ford#3.01.04 [https], medicine.disease, Peptide Fragments, Peptide Fragments/immunology/toxicity, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Gene Expression Regulation, 2808 Neurology, 10033 Clinic for Immunology, biology.protein, 570 Life sciences, Myelin-Oligodendrocyte Glycoprotein, business, 030217 neurology & neurosurgery, Spleen, Epo |
| الوصف: | Background Treatment with erythropoietin (Epo) in experimental autoimmune encephalomyelitis (EAE), the rodent model of multiple sclerosis (MS), has consistently been shown to ameliorate disease progression and improve overall outcome. The effect has been attributed to modulation of the immune response and/or preservation of the central nervous system (CNS) tissue integrity. It remains unclear, however, if (a) Epo acts primarily in the CNS or the periphery and if (b) Epo’s beneficial effect in EAE is mainly due to maintaining CNS tissue integrity or to modulation of the immune response. If Epo acts primarily by modulating the immune system, where is this modulation required? In the periphery, the CNS or both? Methods To address these questions, we used two well-characterized transgenic mouse strains that constitutively overexpress recombinant human Epo (rhEpo) either systemically (tg6) or in CNS only (tg21) in a MOG-induced EAE model. We assessed clinical severity, disease progression, immunomodulation, and CNS tissue integrity, including neuronal survival. Results Although disease onset remained unaffected, EAE progression was alleviated in transgenic animals compared to controls with both lines performing equally well showing that expression of Epo in the periphery is not required; Epo expression in the CNS is sufficient. Immunomodulation was observed in both strains but surprisingly the profile of modulation differed substantially between strains. Modulation in the tg21 strain was limited to a reduction in macrophages in the CNS, with no peripheral immunomodulatory effects observed. In contrast, in the tg6 strain, macrophages were upregulated in the CNS, and, in the periphery of this strain, T cells and macrophages were downregulated. The lack of a consistent immunomodulatory profile across both transgenic species suggests that immunomodulation by Epo is unlikely to be the primary mechanism driving amelioration of EAE. Finally, CNS tissue integrity was affected in all strains. Although myelin appeared equally damaged in all strains, neuronal survival was significantly improved in the spinal cord of tg21 mice, indicating that Epo may ameliorate EAE predominantly by protecting neurons. Conclusions Our data suggests that moderate elevated brain Epo levels provide clinically significant neuroprotection in EAE without modulation of the immune response making a significant contribution. Electronic supplementary material The online version of this article (10.1186/s12974-017-0976-5) contains supplementary material, which is available to authorized users. |
| وصف الملف: | Moransard_J_of_Neuroinflammation_2017.pdf - application/pdf |
| تدمد: | 1742-2094 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d59a7ca3377fc2b6862252dfe1c72b76Test https://pubmed.ncbi.nlm.nih.gov/29029628Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d59a7ca3377fc2b6862252dfe1c72b76 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17422094 |
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