Brain, Vol 120, Issue 3 393-399, Copyright © 1997 by Oxford University Press
B Ferguson, MK Matyszak, MM Esiri and VH Perry
One of the histological hallmarks of early multiple sclerosis lesions is
primary demyelination, with myelin destruction and relative sparing of
axons. On the other hand, it is widely accepted that axonal loss occurs in,
and is responsible for, the permanent disability characterizing the later
chronic progressive stage of the disease. In this study, we have used an
antibody against amyloid precursor protein, known to be a sensitive marker
of axonal damage in a number of other contexts, in immunocytochemical
experiments on paraffin embedded multiple sclerosis lesions of varying ages
in order to see at which stage of the disease axonal damage, in addition to
demyelination, occurs and may thus contribute to the development of
disability in patients. The results show the expression of amyloid
precursor protein in damaged axons within acute multiple sclerosis lesions,
and in the active borders of less acute lesions. This observation may have
implications for the design and timing of therapeutic intervention, one of
the most important aims of which must be the reduction of permanent
disability.
ARTICLES
Axonal damage in acute multiple sclerosis lesions
Department of Pharmacology, Oxford University, UK.
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F G Maggs and J Palace The pathogenesis of multiple sclerosis: is it really a primary inflammatory process? Multiple Sclerosis, June 1, 2004; 10(3): 326 - 329. [Abstract] [PDF]
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C. Lucchinetti and W. Bruck The pathology of primary progressive multiple sclerosis Multiple Sclerosis, June 1, 2004; 10(1_suppl): S23 - S30. [Abstract] [PDF]
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M. J. Craner, J. Newcombe, J. A. Black, C. Hartle, M. L. Cuzner, and S. G. Waxman Molecular changes in neurons in multiple sclerosis: Altered axonal expression of Nav1.2 and Nav1.6 sodium channels and Na+/Ca2+ exchanger PNAS, May 25, 2004; 101(21): 8168 - 8173. [Abstract] [Full Text] [PDF]
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G. C. DeLuca, G. C. Ebers, and M. M. Esiri Axonal loss in multiple sclerosis: a pathological survey of the corticospinal and sensory tracts Brain, May 1, 2004; 127(5): 1009 - 1018. [Abstract] [Full Text] [PDF]
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C. Lucchinetti and W. Bruck The pathology of primary progressive multiple sclerosis Multiple Sclerosis, May 1, 2004; 10(3_suppl): S23 - S30. [Abstract] [PDF]
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R. Nitsch, E. E. Pohl, A. Smorodchenko, C. Infante-Duarte, O. Aktas, and F. Zipp Direct Impact of T Cells on Neurons Revealed by Two-Photon Microscopy in Living Brain Tissue J. Neurosci., March 10, 2004; 24(10): 2458 - 2464. [Abstract] [Full Text] [PDF]
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J. A. Frank, N. Richert, C. Bash, L. Stone, P. A. Calabresi, B. Lewis, R. Stone, T. Howard, and H. F. McFarland Interferon-{beta}-1b slows progression of atrophy in RRMS: Three-year follow-up in NAb- and NAb+ patients Neurology, March 9, 2004; 62(5): 719 - 725. [Abstract] [Full Text] [PDF]
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 E. L. Oleszak, J. R. Chang, H. Friedman, C. D. Katsetos, and C. D. Platsoucas Theiler's Virus Infection: a Model for Multiple Sclerosis Clin. Microbiol. Rev., January 1, 2004; 17(1): 174 - 207. [Abstract] [Full Text] [PDF]
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C. Malmestrom, S. Haghighi, L. Rosengren, O. Andersen, and J. Lycke Neurofilament light protein and glial fibrillary acidic protein as biological markers in MS Neurology, December 23, 2003; 61(12): 1720 - 1725. [Abstract] [Full Text] [PDF]
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A. Diestel, O. Aktas, D. Hackel, I. Hake, S. Meier, C. S. Raine, R. Nitsch, F. Zipp, and O. Ullrich Activation of Microglial Poly(ADP-Ribose)-Polymerase-1 by Cholesterol Breakdown Products during Neuroinflammation: a Link between Demyelination and Neuronal Damage J. Exp. Med., December 1, 2003; 198(11): 1729 - 1740. [Abstract] [Full Text] [PDF]
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D T Chard, P A Brex, O Ciccarelli, C M Griffin, G J M Parker, C Dalton, D R Altmann, A J Thompson, and D H Miller The longitudinal relation between brain lesion load and atrophy in multiple sclerosis: a 14 year follow up study J. Neurol. Neurosurg. Psychiatry, November 1, 2003; 74(11): 1551 - 1554. [Abstract] [Full Text] [PDF]
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 A. C. Lo, C. Y. Saab, J. A. Black, and S. G. Waxman Phenytoin Protects Spinal Cord Axons and Preserves Axonal Conduction and Neurological Function in a Model of Neuroinflammation In Vivo J Neurophysiol, November 1, 2003; 90(5): 3566 - 3571. [Abstract] [Full Text] [PDF]
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G. Pryce, Z. Ahmed, D. J. R. Hankey, S. J. Jackson, J. L. Croxford, J. M. Pocock, C. Ledent, A. Petzold, A. J. Thompson, G. Giovannoni, et al. Cannabinoids inhibit neurodegeneration in models of multiple sclerosis Brain, October 1, 2003; 126(10): 2191 - 2202. [Abstract] [Full Text] [PDF]
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 R. K. Burt, B. A. Cohen, E. Russell, K. Spero, A. Joshi, Y. Oyama, W. J. Karpus, K. Luo, B. Jovanovic, A. Traynor, et al. Hematopoietic stem cell transplantation for progressive multiple sclerosis: failure of a total body irradiation-based conditioning regimen to prevent disease progression in patients with high disability scores Blood, October 1, 2003; 102(7): 2373 - 2378. [Abstract] [Full Text] [PDF]
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L Bo, C A Vedeler, H Nyland, B D Trapp, and S J Mork Intracortical multiple sclerosis lesions are not associated with increased lymphocyte infiltration Multiple Sclerosis, August 1, 2003; 9(4): 323 - 331. [Abstract] [PDF]
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