Early appearance of activated matrix metalloproteinase-9 after focal cerebral ischemia in mice: A possible role in blood-brain barrier dysfunction

被引:333
|
作者
Gasche, Y
Fujimura, M
Morita-Fujimura, Y
Copin, JC
Kawase, M
Massengale, J
Chan, PH
机构
[1] Stanford Univ, Neurosurg Labs, Dept Neurosurg, Palo Alto, CA 94304 USA
[2] Stanford Univ, Neurosurg Labs, Dept Neurol & Neurol Sci, Palo Alto, CA 94304 USA
[3] Stanford Univ, Program Neurosci, Palo Alto, CA 94304 USA
来源
关键词
metalloproteinases; brain; ischemia; vasogenic edema; mice;
D O I
10.1097/00004647-199909000-00010
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
During cerebral ischemia blood-brain barrier (BBB) disruption is a critical event leading to vasogenic edema and secondary brain injury. Gelatinases A and B are matrix metalloproteinases (MMP) able to open the BBB. The current study analyzes by zymography the early gelatinases expression and activation during permanent ischemia in mice (n = 15). ProMMP-9 expression was significantly (P < 0.001) increased in ischemic regions compared with corresponding contralateral regions after 2 hours of ischemia (mean 694.7 arbitrary units [AU], SD +/- 238.4 versus mean 107.6 AU, SD +/- 15.6) and remained elevated until 24 hours (mean 745.7 AU, SD +/- 157.4). Moreover, activated MMP-9 was observed 4 hours after the initiation of ischemia. At the same time as the appearance of activated MMP-9, we detected by the Evan's blue extravasation method a clear increase of BBB permeability. Tissue inhibitor of metalloproteinase-l was not modified during permanent ischemia at any time. The ProMMP-2 was significantly (P < 0.05) increased only after 24 hours of permanent ischemia (mean 213.2 AU, SD +/- 60.6 versus mean 94.6 AU, SD +/- 13.3), and no activated form was observed. The appearance of activated MMP-9 after 4 hours of ischemia in correlation with BBB permeability alterations suggests that MMP-9 may play an active role in early vasogenic edema development after stroke.
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收藏
页码:1020 / 1028
页数:9
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