Peripheral blood levels of matrix metalloproteinase-9 predict lesion volume in acute stroke

被引:38
作者
Ulrich, Nils H. [1 ,2 ]
Dehmel, T. [2 ]
Wittsack, H. J. [3 ]
Kieseier, B. C. [2 ]
Seitz, R. J. [2 ]
机构
[1] Univ Zurich Hosp, Dept Neurosurg, CH-8091 Zurich, Switzerland
[2] Univ Hosp Dusseldorf, Dept Neurol, Dusseldorf, Germany
[3] Univ Hosp Dusseldorf, Inst Diagnost Radiol, Dusseldorf, Germany
关键词
Stroke; Metalloproteinases; MMP-9; Perfusion weighted imaging; Diffusion weighted imaging; Magnetic resonance imaging; FOCAL CEREBRAL-ISCHEMIA; MATRIX METALLOPROTEINASES; INFARCT SIZE; INHIBITION; REPERFUSION; BRAIN; RAT;
D O I
10.1007/s10072-012-0999-8
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Matrix metalloproteinases (MMPs) have been implicated to play an important role in the destruction of the extracellular matrix in diseases of the central nervous system. This study investigated whether the expression of one of these proteases, MMP-9 in blood, is related to the size of human brain infarcts assessed with magnetic resonance imaging. Consecutively, twenty-one acute stroke patients were included prospectively into our study. In blood samples drawn within 24 h after onset, MMP-9 RNA-expression and proteolytic-activity were analyzed by quantitative polymerase chain reaction and gelatin zymography, respectively. The ischemic lesion volumes in time to peak perfusion maps and diffusion weighted imaging were measured morphometrically. RNA-expression levels of MMP-9 in peripheral blood mononuclear cells (PBMCs) correlated with the brain infarct lesion (TTP-delay 4 s, r = -0.61, p = 0.007; TTP-delay 6 s: r = -0.58, p = 0.012; DWI r = -0.47; p = 0.047). Our preliminary results demonstrate that MMP-9 RNA is upregulated in PBMCs in proportion to ischemia. These findings suggest that MMP-9 might contribute to the manifestation of ischemic brain damage. Since MMP-9 is upregulated in acute ischemia inhibition of MMP-9 may represent a complementary treatment target in acute stroke therapy.
引用
收藏
页码:379 / 382
页数:4
相关论文
共 13 条
[1]   Role for matrix metalloproteinase 9 after focal cerebral ischemia, effects of gene knockout and enzyme inhibition with BB-94 [J].
Asahi, M ;
Asahi, K ;
Jung, JC ;
del Zoppo, GJ ;
Fini, ME ;
Lo, EH .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2000, 20 (12) :1681-1689
[2]   ELECTROPHORETIC ANALYSIS OF PLASMINOGEN ACTIVATORS IN POLYACRYLAMIDE GELS CONTAINING SODIUM DODECYL-SULFATE AND COPOLYMERIZED SUBSTRATES [J].
HEUSSEN, C ;
DOWDLE, EB .
ANALYTICAL BIOCHEMISTRY, 1980, 102 (01) :196-202
[3]   Profiles of matrix metalloproteinases, their inhibitors, and laminin in stroke patients - Influence of different therapies [J].
Horstmann, S ;
Kalb, P ;
Koziol, J ;
Gardner, H ;
Wagner, S .
STROKE, 2003, 34 (09) :2165-2170
[4]   Matrix metalloproteinase-9 pretreatment level predicts intracranial hemorrhagic complications after thrombolysis in human stroke [J].
Montaner, J ;
Molina, CA ;
Monasterio, J ;
Abilleira, S ;
Arenillas, JF ;
Ribó, M ;
Quintana, M ;
Alvarez-Sabín, J .
CIRCULATION, 2003, 107 (04) :598-603
[5]   Diffusion-and perfusion-weighted MRI -: The DWI/PWI mismatch region in acute stroke [J].
Neumann-Haefelin, T ;
Wittsack, HJ ;
Wenserski, F ;
Siebler, M ;
Seitz, RJ ;
Mödder, U ;
Freund, HJ .
STROKE, 1999, 30 (08) :1591-1597
[6]   Matrix metalloproteinases as modulators of inflammation and innate immunity [J].
Parks, WC ;
Wilson, CL ;
López-Boado, YS .
NATURE REVIEWS IMMUNOLOGY, 2004, 4 (08) :617-629
[7]   Closure of the blood-brain barrier by matrix metalloproteinase inhibition reduces rtPA-mediated mortality in cerebral ischemia with delayed reperfusion [J].
Pfefferkorn, T ;
Rosenberg, GA .
STROKE, 2003, 34 (08) :2025-2030
[8]   Estimation of gelatinase content in rat brain:: Effect of focal ischemia [J].
Planas, AM ;
Solé, S ;
Justicia, C ;
Farré, ER .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 278 (03) :803-807
[9]   Matrix metalloproteinase expression increases after cerebral focal ischemia in rats - Inhibition of matrix metalloproteinase-9 reduces infarct size [J].
Romanic, AM ;
White, RF ;
Arleth, AJ ;
Ohlstein, EH ;
Barone, FC .
STROKE, 1998, 29 (05) :1020-1030
[10]   Proteolytic cascade enzymes increase in focal cerebral ischemia in rat [J].
Rosenberg, GA ;
Navratil, M ;
Barone, F ;
Feuerstein, G .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1996, 16 (03) :360-366