Acute axonal injury in multiple sclerosis: Correlation with demyelination and inflammation (original) (raw)

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Professor Dr Wolfgang Brück, Institut für Neuropathologie Charité, Campus Virchow-Klinikum, Augustenburger Platz 1, D-13353 Berlin, Germany E-mail: wolfgang.brueck@charite.de

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Revision received:

12 November 1999

Accepted:

17 January 2000

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A. Bitsch, J. Schuchardt, S. Bunkowski, T. Kuhlmann, W. Brück, Acute axonal injury in multiple sclerosis: Correlation with demyelination and inflammation, Brain, Volume 123, Issue 6, June 2000, Pages 1174–1183, https://doi.org/10.1093/brain/123.6.1174
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Abstract

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-α) 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.

APP = amyloid precursor protein, DM = inactive demyelinated lesions, EA = early active demyelinating lesions, ERM = early remyelinating lesions, iNOS = inducible nitric oxide synthase, LA = late active demyelinating lesions, LRM = late remyelinating lesions, MBP = myelin basic protein, MOG = myelin oligodendrocyte glycoprotein, NAA = _N_-acetylaspartate, PLP = proteolipid protein, TNF-α = tumour necrosis factor-alpha, WM = periplaque white matter

© Oxford University Press 2000

Topic:

• tumor necrosis factors
• inflammation
• axon
• inflammation mediators
• macrophages
• multiple sclerosis
• nitric oxide synthase
• t-lymphocytes
• demyelination

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