title: Brain MRI of nasal MOG therapeutic effect in relapsing-progressive EAE.
abstract: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) considered to be a T cell-mediated autoimmune disease. Mucosally administered antigens induce regulatory T cells that secrete anti-inflammatory cytokines at the anatomic site where the mucosally administered Ag is located. We have previously reported in a mouse model of stroke that nasal treatment with MOG35-55 peptide reduces ischemic infarct size and improves behavior, by inducing IL-10-secreting T cells. We have also demonstrated that an experimental autoimmune encephalomyelitis (EAE) model in non-obese diabetic (NOD) mice leads to a relapsing progressive disease and that brain lesions can be visualized noninvasively by magnetic resonance imaging (MRI). Here, we investigated whether nasal treatment with 25μg of MOG35-55 after the first attack affects clinical progression and MRI outcome in the NOD model. We found that nasal MOG35-55 treatment administered three times after the first attack and then weekly reduced both the peak clinical disease score and clinical score during remission. Pathology revealed less infiltration of cells and reduction in white-matter damage as measured by Luxol blue staining in treated animals. This model is unique in that there are lesions in the corpus callosum, external capsule, fimbria, internal capsule and thalamus, which is analogous to what is observed in MS. MRI of individual animals using fractional anisotropy (FA) and T1-gadolinum (T1-Gd) imaging was able to identify lesions in all of these anatomic areas, and we found lower levels of brain pathology by MRI in treated mice with both methods. Our results indicate a beneficial effect of nasal MOG on relapsing-progressive EAE and demonstrate that non-invasive MRI imaging may be used to monitor treatment of ongoing disease in this model for testing new therapies for MS.
authors.affiliation: Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: H
authors.initials: H
authors.lastname: Levy Barazany
authors.affiliation: Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel; Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, UK.
authors.forename: D
authors.initials: D
authors.lastname: Barazany
authors.affiliation: Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: L
authors.initials: L
authors.lastname: Puckett
authors.affiliation: Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Blanga-Kanfi
authors.affiliation: Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Borenstein-Auerbach
authors.affiliation: Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: K
authors.initials: K
authors.lastname: Yang
authors.affiliation: Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Neuroimmune Interactions Laboratory, Department of Immunology, USP, São Paulo, CEP 05508-000, Brazil.
authors.forename: J P
authors.initials: JP
authors.lastname: Peron
authors.affiliation: Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: hweiner@rics.bwh.harvard.edu.
authors.forename: H L
authors.initials: HL
authors.lastname: Weiner
authors.affiliation: Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel. Electronic address: dfrenkel@post.tau.ac.il.
authors.forename: D
authors.initials: D
authors.lastname: Frenkel
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D008279:Magnetic Resonance Imaging; D051379:Mice; D016688:Mice, Inbred NOD; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000494:pharmacology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)
keywords: Brain; DTI; EAE; Fractional anisotropy; MOG; MRI; Multiple sclerosis; NOD mice; Nasal administration; T1-gadolinum; Therapy