Brain, Vol. 123, No. 6, 1174-1183,
June 2000
© 2000 Oxford University Press
Acute axonal injury in multiple sclerosis
Correlation with demyelination and inflammation
1 Departments of Neurology and 2 Neuropathology, Georg-August-Universität, Göttingen, and 3 Department of Neuropathology, Charité, Campus Virchow-Klinikum Berlin, Germany
Correspondence to:
Professor Dr Wolfgang Brück, Institut für Neuropathologie Charité, Campus Virchow-Klinikum, Augustenburger Platz 1, D-13353 Berlin, Germany E-mail: wolfgang.brueck{at}charite.de
Damage to axons is taken as a key factor of disability in multiple sclerosis, but its pathogenesis is largely unknown. Axonal injury is believed to occur as a consequence of demyelination and was recently shown to be a feature even of the early disease stages. The present study was aimed at characterizing the association of axonal injury and histopathological hallmarks of multiple sclerosis such as demyelination, cellular infiltration and expression of inflammatory mediators. Therefore, axon reduction and signs of acute axonal damage were quantified in early lesion development of chronic multiple sclerosis and correlated with demyelinating activity and inflammation. Patients with secondary progressive multiple sclerosis revealed the most pronounced axonal injury, whereas primary progressive multiple sclerosis patients surprisingly showed relatively little acute axonal injury. Acute axonal damage, as defined by the accumulation of amyloid precursor protein (APP), was found to occur not only in active demyelinating but also in remyelinating and inactive demyelinated lesions with a large inter-individual variability. Only few remyelinating lesions were adjacent to areas of active demyelination. In this minority of lesions, axonal damage may have originated from the neighbourhood. APP expression in damaged axons correlated with the number of macrophages and CD8-positive T lymphocytes within the lesions, but not with the expression of tumour necrosis factor-alpha (TNF-
) or inducible nitric oxide synthase (iNOS). Axonal injury is therefore, at least in part, independent of demyelinating activity, and its pathogenesis may be different from demyelination. This has major implications for therapeutic strategies, which aim at preventing both demyelination and axonal loss.
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|
|
|
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|
|
|
 |
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|
|
|
|
|
|
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|
|
|
|
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|
|
|
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|
|
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|
|
|
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|
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|
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|
|
|
|
 |
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|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 H. Krapf, S. P. Morrissey, O. Zenker, T. Zwingers, R. Gonsette, H. -P. Hartung, and the MIMS Study Group Effect of mitoxantrone on MRI in progressive MS: Results of the MIMS trial Neurology, September 13, 2005; 65(5): 690 - 695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 M. Stagi, P. S. Dittrich, N. Frank, A. I. Iliev, P. Schwille, and H. Neumann Breakdown of Axonal Synaptic Vesicle Precursor Transport by Microglial Nitric Oxide J. Neurosci., January 12, 2005; 25(2): 352 - 362. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Kamholz, J. Y. Garbern, O. Gonen, Y. Ge, M. Inglese, and R. I. Grossman Neuronal cell injury precedes brain atrophy in multiple sclerosis Neurology, January 11, 2005; 64(1): 176 - 176. [Full Text] [PDF]
|
|
|
|
|
|
N. Norgren, P. Sundstrom, A. Svenningsson, L. Rosengren, T. Stigbrand, and M. Gunnarsson Neurofilament and glial fibrillary acidic protein in multiple sclerosis Neurology, November 9, 2004; 63(9): 1586 - 1590. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Rejdak, M. J. Eikelenboom, A. Petzold, E. J. Thompson, Z. Stelmasiak, R. H.C. Lazeron, F. Barkhof, C. H. Polman, B. M.J. Uitdehaag, and G. Giovannoni CSF nitric oxide metabolites are associated with activity and progression of multiple sclerosis Neurology, October 26, 2004; 63(8): 1439 - 1445. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J Oh, R G Henry, C Genain, S J Nelson, and D Pelletier Mechanisms of normal appearing corpus callosum injury related to pericallosal T1 lesions in multiple sclerosis using directional diffusion tensor and 1H MRS imaging J. Neurol. Neurosurg. Psychiatry, September 1, 2004; 75(9): 1281 - 1286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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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]
|
|
|
|
|
|
H. J. Kim, I. Ifergan, J. P. Antel, R. Seguin, M. Duddy, Y. Lapierre, F. Jalili, and A. Bar-Or Type 2 Monocyte and Microglia Differentiation Mediated by Glatiramer Acetate Therapy in Patients with Multiple Sclerosis J. Immunol., June 1, 2004; 172(11): 7144 - 7153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Lucchinetti and W. Bruck The pathology of primary progressive multiple sclerosis Multiple Sclerosis, June 1, 2004; 10(1_suppl): S23 - S30. [Abstract] [PDF]
|
|
|
|
|
|
R. R. Kreitman and F. Blanchette On the horizon: possible neuroprotective role for glatiramer acetate Multiple Sclerosis, June 1, 2004; 10(1_suppl): S81 - S89. [Abstract] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
C. Lucchinetti and W. Bruck The pathology of primary progressive multiple sclerosis Multiple Sclerosis, May 1, 2004; 10(3_suppl): S23 - S30. [Abstract] [PDF]
|
|
|
|
|
|
R. R. Kreitman and F. Blanchette On the horizon: possible neuroprotective role for glatiramer acetate Multiple Sclerosis, May 1, 2004; 10(3_suppl): S81 - S89. [Abstract] [PDF]
|
|
|
|
|
|
C. Skulina, S. Schmidt, K. Dornmair, H. Babbe, A. Roers, K. Rajewsky, H. Wekerle, R. Hohlfeld, and N. Goebels Multiple sclerosis: Brain-infiltrating CD8+ T cells persist as clonal expansions in the cerebrospinal fluid and blood PNAS, February 24, 2004; 101(8): 2428 - 2433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Nau, J. Gerber, S. Bunkowski, and W. Bruck Axonal injury, a neglected cause of CNS damage in bacterial meningitis Neurology, February 10, 2004; 62(3): 509 - 511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Lily, J. Palace, and A. Vincent Serum autoantibodies to cell surface determinants in multiple sclerosis: a flow cytometric study Brain, February 1, 2004; 127(2): 269 - 279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Craner, B. C. Hains, A. C. Lo, J. A. Black, and S. G. Waxman Co-localization of sodium channel Nav1.6 and the sodium-calcium exchanger at sites of axonal injury in the spinal cord in EAE Brain, February 1, 2004; 127(2): 294 - 303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
A. Bar-Or, R. K. Nuttall, M. Duddy, A. Alter, H. J. Kim, I. Ifergan, C. J. Pennington, P. Bourgoin, D. R. Edwards, and V. W. Yong Analyses of all matrix metalloproteinase members in leukocytes emphasize monocytes as major inflammatory mediators in multiple sclerosis Brain, December 1, 2003; 126(12): 2738 - 2749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Schroeter, G. Stoll, R. Weissert, H.-P. Hartung, H. Lassmann, and S. Jander CD8+ Phagocyte Recruitment in Rat Experimental Autoimmune Encephalomyelitis: Association with Inflammatory Tissue Destruction Am. J. Pathol., October 1, 2003; 163(4): 1517 - 1524. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Frohman, D. S. Goodin, P. A. Calabresi, J. R. Corboy, P. K. Coyle, M. Filippi, J. A. Frank, S. L. Galetta, R. I. Grossman, K. Hawker, et al. The utility of MRI in suspected MS: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology, September 9, 2003; 61(5): 602 - 611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Vegeto, S. Belcredito, S. Etteri, S. Ghisletti, A. Brusadelli, C. Meda, A. Krust, S. Dupont, P. Ciana, P. Chambon, et al. Estrogen receptor-{alpha} mediates the brain antiinflammatory activity of estradiol PNAS, August 5, 2003; 100(16): 9614 - 9619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Barkhof, W. Bruck, C. J. A. De Groot, E. Bergers, S. Hulshof, J. Geurts, C. H. Polman, and P. van der Valk Remyelinated Lesions in Multiple Sclerosis: Magnetic Resonance Image Appearance Arch Neurol, August 1, 2003; 60(8): 1073 - 1081. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. G. Geurts, G. Wolswijk, L. Bo, P. van der Valk, C. H. Polman, D. Troost, and E. Aronica Altered expression patterns of group I and II metabotropic glutamate receptors in multiple sclerosis Brain, August 1, 2003; 126(8): 1755 - 1766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Giuliani, C. G. Goodyer, J. P. Antel, and V. W. Yong Vulnerability of Human Neurons to T Cell-Mediated Cytotoxicity J. Immunol., July 1, 2003; 171(1): 368 - 379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Wolswijk and R. Balesar Changes in the expression and localization of the paranodal protein Caspr on axons in chronic multiple sclerosis Brain, July 1, 2003; 126(7): 1638 - 1649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H Lassmann Axonal injury in multiple sclerosis J. Neurol. Neurosurg. Psychiatry, June 1, 2003; 74(6): 695 - 697. [Full Text] [PDF]
|
|
|
|
|
|
N. De Stefano, P. M. Matthews, M. Filippi, F. Agosta, M. De Luca, M. L. Bartolozzi, L. Guidi, A. Ghezzi, E. Montanari, A. Cifelli, et al. Evidence of early cortical atrophy in MS: Relevance to white matter changes and disability Neurology, April 8, 2003; 60(7): 1157 - 1162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Castriota-Scanderbeg, F. Fasano, G. Hagberg, U. Nocentini, M. Filippi, and C. Caltagirone Coefficient Dav Is More Sensitive Than Fractional Anisotropy in Monitoring Progression of Irreversible Tissue Damage in Focal Nonactive Multiple Sclerosis Lesions AJNR Am. J. Neuroradiol., April 1, 2003; 24(4): 663 - 670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rodriguez A function of myelin is to protect axons from subsequent injury: implications for deficits in multiple sclerosis Brain, April 1, 2003; 126(4): 751 - 752. [Full Text] [PDF]
|
|
|
|
|
|
I. Tsunoda, L.-Q. Kuang, J. E. Libbey, and R. S. Fujinami Axonal Injury Heralds Virus-Induced Demyelination Am. J. Pathol., April 1, 2003; 162(4): 1259 - 1269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. M. Medana and M. M. Esiri Axonal damage: a key predictor of outcome in human CNS diseases Brain, March 1, 2003; 126(3): 515 - 530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Buckle, P. Hollsberg, and D. A. Hafler Activated CD8+ T cells in secondary progressive MS secrete lymphotoxin Neurology, February 25, 2003; 60(4): 702 - 705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Nicot, P. V. Ratnakar, Y. Ron, C.-C. Chen, and S. Elkabes Regulation of gene expression in experimental autoimmune encephalomyelitis indicates early neuronal dysfunction Brain, February 1, 2003; 126(2): 398 - 412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
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D. Buljevac, H. Z. Flach, W. C. J. Hop, D. Hijdra, J. D. Laman, H. F. J. Savelkoul, F. G. A. van der Meche, P. A. van Doorn, and R. Q. Hintzen Prospective study on the relationship between infections and multiple sclerosis exacerbations Brain, May 1, 2002; 125(5): 952 - 960. [Abstract] [Full Text] [PDF]
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W Bruck, C Lucchinetti, and H Lassmann The pathology of primary progressive multiple sclerosis Multiple Sclerosis, April 1, 2002; 8(2): 93 - 97. [Abstract] [PDF]
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M. Rottnek, A. Di Rocco, D. Laudier, and S. Morgello Axonal damage is a late component of vacuolar myelopathy Neurology, February 12, 2002; 58(3): 479 - 481. [Abstract] [Full Text] [PDF]
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C. Stadelmann, M. Kerschensteiner, T. Misgeld, W. Bruck, R. Hohlfeld, and H. Lassmann BDNF and gp145trkB in multiple sclerosis brain lesions: neuroprotective interactions between immune and neuronal cells? Brain, January 1, 2002; 125(1): 75 - 85. [Abstract] [Full Text] [PDF]
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N. Scolding Regenerating myelin Brain, November 1, 2001; 124(11): 2129 - 2130. [Full Text] [PDF]
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T. A. Newman, S. T. Woolley, P. M. Hughes, N. R. Sibson, D. C. Anthony, and V. H. Perry T-cell- and macrophage-mediated axon damage in the absence of a CNS-specific immune response: involvement of metalloproteinases Brain, November 1, 2001; 124(11): 2203 - 2214. [Abstract] [Full Text] [PDF]
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C. Trebst, T. Lykke Sorensen, P. Kivisakk, M. K. Cathcart, J. Hesselgesser, R. Horuk, F. Sellebjerg, H. Lassmann, and R. M. Ransohoff CCR1+/CCR5+ Mononuclear Phagocytes Accumulate in the Central Nervous System of Patients with Multiple Sclerosis Am. J. Pathol., November 1, 2001; 159(5): 1701 - 1710. [Abstract] [Full Text] [PDF]
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T. L. Sorensen and F. Sellebjerg Distinct chemokine receptor and cytokine expression profile in secondary progressive MS Neurology, October 23, 2001; 57(8): 1371 - 1376. [Abstract] [Full Text] [PDF]
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N. Evangelou, D. Konz, M. M. Esiri, S. Smith, J. Palace, and P. M. Matthews Size-selective neuronal changes in the anterior optic pathways suggest a differential susceptibility to injury in multiple sclerosis Brain, September 1, 2001; 124(9): 1813 - 1820. [Abstract] [Full Text] [PDF]
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I. Medana, M. A. Martinic, H. Wekerle, and H. Neumann Transection of Major Histocompatibility Complex Class I-Induced Neurites by Cytotoxic T Lymphocytes Am. J. Pathol., September 1, 2001; 159(3): 809 - 815. [Abstract] [Full Text] [PDF]
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 A. A. Dandekar, G. F. Wu, L. Pewe, and S. Perlman Axonal Damage Is T Cell Mediated and Occurs Concomitantly with Demyelination in Mice Infected with a Neurotropic Coronavirus J. Virol., July 1, 2001; 75(13): 6115 - 6120. [Abstract] [Full Text] [PDF]
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B. Kornek, M. K. Storch, J. Bauer, A. Djamshidian, R. Weissert, E. Wallstroem, A. Stefferl, F. Zimprich, T. Olsson, C. Linington, et al. Distribution of a calcium channel subunit in dystrophic axons in multiple sclerosis and experimental autoimmune encephalomyelitis Brain, June 1, 2001; 124(6): 1114 - 1124. [Abstract] [Full Text] [PDF]
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D. P. Auer, T. Schirmer, J. O. Heidenreich, J. Herzog, B. Putz, and M. Dichgans Altered white and gray matter metabolism in CADASIL: A proton MR spectroscopy and 1H-MRSI study Neurology, March 13, 2001; 56(5): 635 - 642. [Abstract] [Full Text] [PDF]
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M Filippi Enhanced magnetic resonance imaging in multiple sclerosis Multiple Sclerosis, October 1, 2000; 6(5): 320 - 326. [Abstract] [PDF]
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J. H. Noseworthy, C. Lucchinetti, M. Rodriguez, and B. G. Weinshenker Multiple Sclerosis N. Engl. J. Med., September 28, 2000; 343(13): 938 - 952. [Full Text] [PDF]
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