title: Focal immune-mediated white matter demyelination reveals an age-associated increase in axonal vulnerability and decreased remyelination efficiency.
abstract: In addition to being an established risk factor for neurodegenerative diseases, age is increasingly recognized as adversely influencing regeneration. Accumulating evidence also suggests that age plays important, although poorly understood, roles with respect to course and prognosis in the degenerative and untreatable later phase of multiple sclerosis. Two experimental models of multiple sclerosis have been particularly influential in modeling the different aspects of neuronal injury and regeneration: global experimental autoimmune encephalomyelitis and focal toxin-mediated injury. Against this background, we report a focal model of immune-mediated demyelinating injury that reliably generates targeted primary demyelination and axonal injury. A detailed pathologic characterization of this model, modified extensively from an earlier study, showed that aged adult animals exhibited increased vulnerability to axonal injury and reduced efficiency of remyelination compared with younger animals. More important, remyelination in aged animals was predominantly Schwann cell mediated, in contrast to the central oligodendrocyte-mediated remyelination that predominated in younger rodents. Together, these findings establish an experimental platform to further study the influence of age on injury and repair in a biologically relevant model of human demyelinating injury.
authors.affiliation: Euan MacDonald Centre for Motor Neurone Disease Research, Centre for Neuroregeneration, University of Edinburgh, Edinburgh, United Kingdom. dhampton@staffmail.ed.ac.uk
authors.forename: David W
authors.initials: DW
authors.lastname: Hampton
authors.forename: Neill
authors.initials: N
authors.lastname: Innes
authors.forename: Doron
authors.initials: D
authors.lastname: Merkler
authors.forename: Chao
authors.initials: C
authors.lastname: Zhao
authors.forename: Robin J M
authors.initials: RJ
authors.lastname: Franklin
authors.forename: Siddharthan
authors.initials: S
authors.lastname: Chandran
mesh_terms: D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000648:ultrastructure*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D008854:Microscopy, Electron; D009185:Myelin Proteins / Q000276:immunology; D009186:Myelin Sheath / Q000502:physiology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009416:Nerve Regeneration / Q000502:physiology*; D009836:Oligodendroglia / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D011917:Rats, Inbred Lew; D012583:Schwann Cells / Q000502:physiology / Q000648:ultrastructure; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: C571326:MOG protein, human; C571328:Mog protein, rat; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma