Early appearance of activated matrix metalloproteinase-9 after focal cerebral ischemia in mice: a possible role in blood-brain barrier dysfunction.
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-1 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.
Gasche
Y
Y
Department of Neurosurgery, Stanford University, Palo Alto, California, USA.
Fujimura
M
M
Morita-Fujimura
Y
Y
Copin
J C
JC
Kawase
M
M
Massengale
J
J
Chan
P H
PH
D000818:Animals; D001812:Blood-Brain Barrier; D002545:Brain Ischemia / Q000201:enzymology*; D017364:Collagenases / Q000378:metabolism*; D004789:Enzyme Activation; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9; D051379:Mice
D017364:Collagenases; D020780:Matrix Metalloproteinase 9