White matter extracellular matrix chondroitin sulfate/dermatan sulfate proteoglycans in multiple sclerosis

被引:128
|
作者
Sobel, RA
Ahmed, AS
机构
[1] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA
[2] Vet Affairs Hlth Care Syst, Palo Alto, CA USA
[3] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA
来源
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY | 2001年 / 60卷 / 12期
关键词
axons; demyelination; extracellular matrix; inflammation; multiple selerosis; neuroimaging; proteoglycans;
D O I
10.1093/jnen/60.12.1198
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 component,,. 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.
引用
收藏
页码:1198 / 1207
页数:10
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