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Cystatin C expression in ischemic white matter lesions.

Authors: Umegae, N  Nagai, A  Terashima, M  Watanabe, T  Shimode, K  Kobayashi, S  Masuda, J  Kim, SU  Yamaguchi, S 
Citation: Umegae N, etal., Acta Neurol Scand. 2008 Jul;118(1):60-7.
Pubmed: (View Article at PubMed) PMID:18261165
DOI: Full-text: DOI:10.1111/j.1600-0404.2007.00984.x

OBJECTIVES: To study the involvement of cystatin C in the progression of ischemic white matter lesions (WMLs). MATERIALS AND METHODS: Cystatin C levels in the cerebrospinal fluid (CSF) of patients with cerebrovascular disease, and also in primary and established human neural cell cultures were investigated. For pathologic analysis, cystatin C immunoreactivity was investigated in the white matter of patients with severe WMLs, mild WMLs or controls. RESULTS: Cystatin C levels in the CSF of patients with Fazekas WML grade 3 [14 with hypertension; W/HT(+) and nine without hypertension; W/HT(-)] were lower than those in 38 patients with grade 0-1 (P = 0.0022 and P < 0.0001 respectively). Immunohistochemical study showed that the cystatin C immunoreactivity was found in astrocytes, and the number of astrocytes in the white matter in the severe WML group was decreased when compared with that in controls (P = 0.0027) and in the mild WML group (P = 0.0024). In human neural cell cultures, treatments with thrombin, matrix metalloproteinases and interleukin 1 beta increased the expression of cystatin C mRNA in human astrocytes and hybrid neurons, but an enzyme-linked immunosorbent assay revealed that only thrombin significantly increased the production and secretion of cystatin C in astrocytes. CONCLUSIONS: These results suggest that low levels of CSF cystatin C in ischemic WMLs might be due to the decreased number of astrocytes that secrete cystatin C in response to the stimuli of proteases and inflammatory cytokines.

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CRRD Object Information
CRRD ID: 2314349
Created: 2009-11-11
Species: All species
Last Modified: 2009-11-11
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.