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White Matter Extracellular Matrix Chondroitin Sulfate/Dermatan Sulfate Proteoglycans in Multiple Sclerosis
- Source :
- Journal of Neuropathology & Experimental Neurology. 60:1198-1207
- Publication Year :
- 2001
- Publisher :
- Oxford University Press (OUP), 2001.
-
Abstract
- Extracellular matrix (ECM) alterations in the central nervous system (CNS) of multiple sclerosis (MS) patients result from blood-brain barrier breakdown, release and activation of proteases, and synthesis of ECM components. To elucidate their potential pathophysiologic roles, we analyzed expression of major CNS ECM proteoglycans (PGs) in MS and control CNS tissues. In active MS plaque edges, 3 CNS lecticans (versican, aggrecan, and neurocan) and dermatan sulfate PG were increased in association with astrocytosis; in active plaque centers they were decreased in the ECM and accumulated in foamy macrophages, suggesting that these ECM PGs are injured and phagocytosed along with myelin. In inactive lesions they were diminished and in normal-appearing white matter they showed heretofore-unappreciated abnormal heterogeneous aggregation. Phosphacan, an ECM PG abundant in both gray and white matter, was less markedly altered. Since in development the spaciotemporal expression of ECM PGs influences neurite outgrowth, cell migration, axon guidance, and myelination, these data suggest that 1) enhanced white matter lectican and dermatan sulfate PG expression in the pro-inflammatory milieu of expanding lesion edges contributes to their sharp boundaries and the failure of neuronal ingrowth; 2) decreases in plaque centers may preclude regeneration and repair; and 3) diffuse ECM PG damage relates to axon degeneration outside of overt lesions. Thus, ECM PG alterations are specific, temporally dynamic, and widespread in MS patients and may play critical roles in lesion pathogenesis and CNS dysfunction.
- Subjects :
- Adult
Male
Pathology
medicine.medical_specialty
Multiple Sclerosis
Adolescent
Dermatan Sulfate
Dermatan sulfate
Pathology and Forensic Medicine
Extracellular matrix
Mice
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Myelin
Neurocan
medicine
Animals
Humans
Lectican
Chondroitin sulfate
Child
Aggrecan
Aged
Aged, 80 and over
Brain Chemistry
biology
Brain
General Medicine
Middle Aged
Immunohistochemistry
Extracellular Matrix
medicine.anatomical_structure
Chondroitin Sulfate Proteoglycans
Neurology
chemistry
biology.protein
Versican
Female
Neurology (clinical)
Subjects
Details
- ISSN :
- 15546578 and 00223069
- Volume :
- 60
- Database :
- OpenAIRE
- Journal :
- Journal of Neuropathology & Experimental Neurology
- Accession number :
- edsair.doi.dedup.....1b64bfaf223a18dbfe2e99a5551b1220
- Full Text :
- https://doi.org/10.1093/jnen/60.12.1198