title: A characterization of white matter pathology following spinal cord compression injury in the rat.
abstract: Our laboratory has previously described the characteristics of neuronal injury in a rat compression model of spinal cord injury (SCI), focussing on the impact of this injury on the gray matter. However, white matter damage is known to play a critical role in functional outcome following injury. Therefore, in the present study, we used immunohistochemistry and electron microscopy to examine the alterations to the white matter that are initiated by compression SCI applied at T12 vertebral level. A significant loss of axonal and dendritic cytoskeletal proteins was observed at the injury epicenter within 1day of injury. This was accompanied by axonal dysfunction, as demonstrated by the accumulation of β-amyloid precursor protein (β-APP), with a peak at 3days post-SCI. A similar, acute loss of cytoskeletal proteins was observed up to 5mm away from the injury epicenter and was particularly evident rostral to the lesion site, whereas β-APP accumulation was prominent in tracts proximal to the injury. Early myelin loss was confirmed by myelin basic protein (MBP) immunostaining and by electron microscopy, which also highlighted the infiltration of inflammatory and red blood cells. However, 6weeks after injury, areas of new Schwann cell and oligodendrocyte myelination were observed. This study demonstrates that substantial white matter damage occurs following compression SCI in the rat. Moreover, the loss of cytoskeletal proteins and accumulation of β-APP up to 5mm away from the lesion site within 1day of injury indicates the rapid manner in which the axonal damage extends in the rostro-caudal axis. This is likely due to both Wallerian degeneration and spread of secondary cell death, with the latter affecting axons both proximal and distal to the injury.
authors.affiliation: Centre for Neuroscience and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK. Electronic address: emailrache@yahoo.co.uk.
authors.forename: R E
authors.initials: RE
authors.lastname: Ward
authors.affiliation: Centre for Neuroscience and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK; The Institute of Medical Sciences, School of Medical Science, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: W
authors.initials: W
authors.lastname: Huang
authors.affiliation: Centre for Neuroscience and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
authors.forename: M
authors.initials: M
authors.lastname: Kostusiak
authors.affiliation: Centre for Neuroscience and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
authors.forename: P N
authors.initials: PN
authors.lastname: Pallier
authors.affiliation: Centre for Neuroscience and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
authors.forename: A T
authors.initials: AT
authors.lastname: Michael-Titus
authors.affiliation: Centre for Neuroscience and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
authors.forename: J V
authors.initials: JV
authors.lastname: Priestley
mesh_terms: D000818:Animals; D005260:Female; D009413:Nerve Fibers, Myelinated / Q000648:ultrastructure*; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013117:Spinal Cord Compression / Q000473:pathology*; D013904:Thoracic Vertebrae
chemical_list: D016900:Neurofilament Proteins
keywords: CST; DC; DLWM; FITC; IR; MAP-2; MBP; NF-200; PB; PBS; PFA; PO; SCI; TRITC; VLWM; VWM; axons; compression injury; corticospinal tract; demyelination; dorsal column; dorsolateral white matter; fluorescein isothiocyanate; immunoreactivity; microtubule associated protein-2; myelin basic protein; neurofilament; neurofilament-200; paraformaldehyde; phosphate buffer; phosphate-buffered saline; propylene oxide; spinal cord injury; tetramethylrhodamine isothiocyanate; ventral white matter; ventrolateral white matter; white matter; β-APP; β-amyloid precursor protein