The pathology of multiple sclerosis is location-dependent: no significant complement activation is detected in purely cortical lesions
Abstract
Complement activation is known to occur in white matter multiple sclerosis (MS) lesions. It is thought to mediate oligodendrocyte/myelin damage and to be a marker of pathologic heterogeneity among individuals. Less is known about complement deposition in the gray matter in MS. The aim of this study was to characterize the presence and distribution of complement activation products in cortical MS lesions. Immunohistochemical staining was performed on cryostat sections from the brains of 22 MS patients and 5 nonneurologic control patients obtained at autopsy. Deposition of the complement activation products C1q, C3d, and C5b-9 (membrane attack complex) was detected on and within macrophages/microglia and astrocytes and in blood vessel walls in white matter MS lesions. C3d and C4d were detected along myelin sheaths at the edge of the lesions. In the gray matter part of combined gray matter/white matter lesions complement activation was less frequent, but increased immunopositivity was detected for C3d on blood vessels, and for C3d and C4d on myelin at the border of lesions, when compared with control areas. In contrast, in the purely cortical lesions, the extent of complement deposition in general was low. In conclusion, the role of complement in MS pathogenesis seems lesion location-dependent.
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Pure cortical lesions in post-mortem tissues show little or no inflammation.
“This may well reflect the greater microglia and astrocyte activity in the white matter; pure cortical lesions in post-mortem tissues show little or no inflammation (Bo et al., 2004; Brink et al., 2005; van Horssen et al., 2007), although early lesions have been associated with prominent microglial activation (Lucchinetti et al., 2011).”
From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as Brink et al., 2005
The increased TSPO expression in leukocortical lesions but not other grey matter lesions may reflect the greater microglia and astrocyte activity in the white matter.
“This may well reflect the greater microglia and astrocyte activity in the white matter; pure cortical lesions in post-mortem tissues show little or no inflammation (Bo et al., 2004; Brink et al., 2005; van Horssen et al., 2007), although early lesions have been associated with prominent microglial activation (Lucchinetti et al., 2011).”
From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as Brink et al., 2005
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“These symptoms and signs may be caused by axonal and neuronal loss in the cortex (5).”
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Kuhlmann, T., Ludwin, S., Prat, A., Antel, J., Brück, W., & Lassmann, H. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1653-y · Cited by 692 · see citing works
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A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis
Nutma, E., Stephenson, J. A., Gorter, R. P., de Bruin, J., Boucherie, D. M., Donat, C. K., Breur, M., van der Valk, P., Matthews, P. M., Owen, D. R., et al. (2019) · Brain · doi:10.1093/brain/awz287 · Cited by 138 · see citing works
“…microglia and astrocyte activity in the white matter; pure cortical lesions in post-mortem tissues show little or no inflammation (Bo et al. , 2004; Brink et al. , 2005; van Horssen et al. , 2007), although early lesions have been associated with prominent microglial activation (Lucchinetti et…”
The cuprizone model: regional heterogeneity of pathology
Wergeland, S., Torkildsen, Ø., Myhr, K., Mørk, S. J., & Bø, L. (2012) · APMIS · doi:10.1111/j.1600-0463.2012.02882.x · Cited by 52 · see citing works
Self-citation
- Authors
- Brink, B. P., Veerhuis, R., Breij, E. C. W., van der Valk, P., Dijkstra, C. D., & Bö, L.
- Affiliations
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-02
- Volume
- 64
- Issue
- 2
- Pages
- 147-155
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W1259091075
- Cited by
- 191
- References
- 4
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 7 · 2021: 4 · 2020: 8 · 2019: 8 · 2018: 5 · 2017: 9 · 2016: 8 · 2015: 12 · 2014: 12 · 2013: 13 · 2012: 14
- FWCI
- 9.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- multiple sclerosis, complement activation, cortical lesions, gray matter, white matter lesions, C1q, C3d, C4d, membrane attack complex, myelin damage, microglia, macrophages, astrocytes, complement deposition
- MeSH terms
- Adult, Aged, Brain, Complement Activation, Female, Humans, Immunohistochemistry, Male, Middle Aged, Multiple Sclerosis, Peptide Fragments, Complement C1q, Complement C3d, Complement C4b, Complement Membrane Attack Complex
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