Cystatin C expression in ischemic white matter lesions.
ABSTRACT To study the involvement of cystatin C in the progression of ischemic white matter lesions (WMLs).
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.
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.
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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ABSTRACT: The aim of this study was to investigate the changes in the levels of cystatin C, which protects neurodegeneration in the central nervous system with the inhibition of cysteine protease and by inducing autophagy in the pathogenesis of cerebral vasospasm and levels of vasoconstrictive neuropeptid Y (NPY) in the brain tissue homogenates of rat model of subarachnoid hemorrhage (SAH). Three experimental groups were used: Day 2 and Day 7 groups after SAH, and also a control group. There were seven Wistar albino rats in each group. SAH was accomplished by transclival basilar artery puncture. Rat cystatin C, rat NPY were determined with ELISA in brain tissue homogenates. Day 2 group showed significantly enhanced cystatin C values in comparision with the control group (P=0.048). NPY levels between the Day 2 and Day 7 groups and the control groups were not significantly different (P=0.315). In histopathological examination, there was less neuronal loss in the Day 2 group than in the Day 7 group. Regarding our results, it would be more valuable to measure NPY levels in specific brain areas. The increased cystatin C levels on the second day after SAH is probably a pathophysiologic mechanism to organize protease activity.Acta biochimica Polonica 12/2014; 61(4). · 1.39 Impact Factor
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ABSTRACT: AIM: To investigate the changes of cerebrospinal fluid (CSF) cystatin C (CC) levels associated with the postoperative ischemic conditions and prognostic outcome in patients with aneurysmal subarachnoid hemorrhage (SAH). MATERIAL and METHODS: The study group consisted of 40 patients with microsurgically clipped intracranial aneurysms (IA's) and 22 control CSF samples. In patients, CSF samples were taken from the lumbar intrathecal catheter for CC measurement, at the beginning of operation, immediately after the operation (early postoperative), and the first postoperative day (late postoperative). RESULTS: CC levels in three periods were significantly higher in patients with Hunt-Hess scores of 4,5 than 1, 2, 3. There was a significant difference between the CC concentrations on the first postoperative day and controls. In patients who developed focal cerebral ischemia, CC levels at early and late postoperative periods were significantly higher than the group without ischemia. In addition, patients with poor prognostic outcome (GOS score of 1, 2, 3) had significantly higher levels of CC in all three periods than that of patients with good outcome (GOS score of 4, 5). CONCLUSION: The raised CSF CC concentrations appear to be associated with the severity of bleeding, intraoperative ischemic events and poor prognostic outcome in patients with aneurysmal SAH.Turkish neurosurgery 05/2014; 24(3):391-7. DOI:10.5137/1019-5149.JTN.8953-13.1 · 0.53 Impact Factor
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ABSTRACT: Extracellular vesicles (EVs) and their protein levels have been identified as a potential risk marker for the development of vascular disease. In the present study, we assessed whether levels of four previously identified EV proteins (cystatin C, serpin G1, serpin F2 and CD14) are associated with cerebral white matter lesions (WMLs) and brain atrophy. Cohort study; cross-sectional and prospective. Single centre, secondary and tertiary setting. 1309 patients with manifest vascular disease from the Second Manifestations of ARTerial disease-MR (SMART-MR) study, of which 994 had successful brain MRI and EV protein level measurements. WML and brain parenchymal fraction (BPF), as parameter for brain atrophy, at baseline and follow-up. The relationship between EV protein levels and WML volume (expressed as log transformed percentage of intracranial volume) and BPF (expressed percentage of intracranial volume) on 1.5 T brain MRI was assessed with multivariable linear regression modelling. Subsequently, the relationship between baseline EV protein levels and progression of atrophy and WML was analysed in 534 patients, in whom a follow-up MRI was obtained after 4 years. Higher EV-cystatin C and EV-CD14 were significantly associated with larger WML volume (linear regression coefficient (95% CI) 0.10 log %/SD (0.04 to 0.17) and 0.14 log %/SD (0.07 to 0.20), respectively. Higher EV-CD14 was associated with more brain atrophy (-0.14%/SD; -0.27 to -0.01). Baseline EV-CD14 was significantly associated with increase of WMLs (0.11 log %/SD (0.04 to 0.18)). No relationship with EV-serpins was observed at baseline or at follow-up. EV proteins cystatin C and CD14 are related to cerebral WMLs and the progression of brain atrophy in patients with manifest vascular disease, potentially identifying EVs in the aetiology of structural brain changes.BMJ Open 01/2014; 4(1):e003824. DOI:10.1136/bmjopen-2013-003824 · 2.06 Impact Factor