title: No evidence for chronic demyelination in spared axons after spinal cord injury in a mouse.
abstract: The pattern of remyelination after traumatic spinal cord injury remains elusive, with animal and human studies reporting partial to complete demyelination followed by incomplete remyelination. In the present study, we found that spared rubrospinal tract (RST) axons of passage traced with actively transported dextrans and examined caudally to the lesion 12 weeks after mouse spinal cord contusion injury were fully remyelinated. Spared axons exhibited a marginally reduced myelin thickness and significantly shorter internodes. CASPR (contactin-associated protein) and K(v)1.2 channels were used to identify internodes and paranodal protein distribution properties were used as an index of myelin integrity. This is the first time the CNS myelin internode length was measured in a mouse. To better understand the significance of shortened internodes and thinner myelin in spared axons, we modeled conduction properties using McIntyre's et al. model of myelinated axons. Mathematical modeling predicted a 21% decrease in the conduction velocity of remyelinated RST axons attributable to shortened internodes. To determine whether demyelination could be present on axons exhibiting a pathological transport system, we used the retroviral reporter system. Virally delivered green fluorescent protein unveiled a small population of dystrophic RST axons that persist chronically with evident demyelination or abnormal remyelination. Collectively, these data show that lasting demyelination in spared axons is rare and that remyelination of axons of passage occurs in the chronically injured mouse spinal cord.
authors.affiliation: Department of Neurological Surgery, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Jurate
authors.initials: J
authors.lastname: Lasiene
authors.forename: Larry
authors.initials: L
authors.lastname: Shupe
authors.forename: Steve
authors.initials: S
authors.lastname: Perlmutter
authors.forename: Philip
authors.initials: P
authors.lastname: Horner
mesh_terms: D000818:Animals; D001369:Axons / Q000648:ultrastructure*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D051663:Kv1.2 Potassium Channel / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D016253:Microscopy, Immunoelectron; D008959:Models, Neurological; D009186:Myelin Sheath / Q000648:ultrastructure*; D009416:Nerve Regeneration; D009431:Neural Conduction; D011930:Reaction Time; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors; D014162:Transfection
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C491322:Cntnap1 protein, mouse; D051663:Kv1.2 Potassium Channel; D049452:Green Fluorescent Proteins