A characterization of white matter pathology following spinal cord compression injury in the rat

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• 作者：R.E. Ward ; W. Huang ; M. Kostusiak ; P.N. Pallier ; A.T. Michael-Titus ; J.V. Priestley
• 关键词：尾-APP ; 尾-amyloid precursor protein ; CST ; corticospinal tract ; DC ; dorsal column ; DLWM ; dorsolateral white matter ; FITC ; fluorescein isothiocyanate ; IR ; immunoreactivity ; MAP-2 ; microtubule associated protein-2 ; MBP ; myelin basic protein ; NF-200 ; neurofilament-200 ; PB ; phosphate buffer ; PBS ; phosphate-buffered saline ; PFA ; paraformaldehyde ; PO ; propylene oxide ; SCI ; spinal cord injury ; TRITC ; tetramethylrhodamine isothiocyanate ; VLWM ; ventrolateral white matter ; VWM ; ventral white matter
• 刊名：Neuroscience
• 出版年：28 February, 2014
• 年：2014
• 卷：260
• 期：Complete
• 页码：227-239
• 全文大小：5245 K

文摘

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 1 day of injury. This was accompanied by axonal dysfunction, as demonstrated by the accumulation of 尾-amyloid precursor protein (尾-APP), with a peak at 3 days post-SCI. A similar, acute loss of cytoskeletal proteins was observed up to 5 mm away from the injury epicenter and was particularly evident rostral to the lesion site, whereas 尾-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, 6 weeks 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 尾-APP up to 5 mm away from the lesion site within 1 day 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.