title: Early axonal damage and progressive myelin pathology define the kinetics of CNS histopathology in a mouse model of multiple sclerosis.
abstract: Studies of MS histopathology are largely dependent on suitable animal models. While light microscopic analysis gives an overview of tissue pathology, it falls short in evaluating detailed changes in nerve fiber morphology. The ultrastructural data presented here and obtained from studies of myelin oligodendrocyte glycoprotein (MOG):35-55-induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice delineate that axonal damage and myelin pathology follow different kinetics in the disease course. While myelin pathology accumulated with disease progression, axonal damage coincided with the initial clinical disease symptoms and remained stable over time. This pattern applied both to irreversible axolysis and early axonal pathology. Notably, these histopathological patterns were reflected by the normal-appearing white matter (NAWM), suggesting that the NAWM is also in an active neurodegenerative state. The data underline the need for neuroprotection in MS and suggest the MOG model as a highly valuable tool for the assessment of different therapeutic strategies.
authors.affiliation: Department of Anatomy I, Joseph-Stelzmann-Str. 9, University of Cologne, 50931 Cologne, Germany.
authors.forename: Mascha S
authors.initials: MS
authors.lastname: Recks
authors.forename: Eva R
authors.initials: ER
authors.lastname: Stormanns
authors.forename: Jonas
authors.initials: J
authors.lastname: Bader
authors.forename: Stefan
authors.initials: S
authors.lastname: Arnhold
authors.forename: Klaus
authors.initials: K
authors.lastname: Addicks
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kuerten
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology / Q000648:ultrastructure; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology*; D005260:Female; D007700:Kinetics; D008159:Lumbar Vertebrae; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology*; D004676:Myelin Basic Protein / Q000276:immunology; D018991:Myelin Proteolipid Protein / Q000276:immunology; D009186:Myelin Sheath / Q000473:pathology / Q000648:ultrastructure; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013116:Spinal Cord / Q000473:pathology / Q000648:ultrastructure
chemical_list: C101821:MP4 protein, chimeric; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C445081:myelin oligodendrocyte glycoprotein (35-55); C094242:myelin proteolipid protein (178-191)
keywords: 4% paraformaldehyde/4% glutaraldehyde; Axonal pathology;; B6; C57BL/6; CFA; CNS; CST; DC; EAE; EAE;; Electron microscopy;; FGF; IFA; MBP; MBP-PLP fusion protein; MOG; MOG:35–55;; MP4; MS; NAWM; NNND; Neurodegeneration;; OPC; PFA-GA; PLP; VLC; central nervous system; complete Freund's adjuvant; corticospinal tract; dorsal column; experimental autoimmune encephalomyelitis; fibroblast growth factor; incomplete Freund's adjuvant; multiple sclerosis; myelin basic protein; myelin oligodendrocyte glycoprotein; nearest neighbor neurofilament distance; normal-appearing white matter; oligodendrocyte precursor cells; proteolipid protein; ventrolateral column