Cystatin C expression in ischemic white matter lesions.
OBJECTIVE
To study the involvement of cystatin C in the progression of ischemic white matter lesions (WMLs).


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.
Umegae
N
N
Department of Internal Medicine III, University Hospital, Shimane University, Izumo, Japan.
Nagai
A
A
Terashima
M
M
Watanabe
T
T
Shimode
K
K
Kobayashi
S
S
Masuda
J
J
Kim
S U
SU
Yamaguchi
S
S
D000368:Aged; D000369:Aged, 80 and over; D001253:Astrocytes / Q000378:metabolism; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D055316:Cystatin C; D015891:Cystatins / Q000378:metabolism*; D048909:Diabetes Complications / Q000150:complications / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism
C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins