Differential alterations in the expression and activity of matrix metalloproteinases 2 and 9 after transient cerebral ischemia in mice.
Abnormal expression and activity of matrix metalloproteinases (MMPs) may contribute to the pathophysiology of cerebral disease such as ischemic injury. In this study, we compared the cellular localization, expression, and activity of MMP-2 and -9 in relation to the evolution of neuronal damage 24 and 72 h after transient global ischemia. In response to ischemia, there was a generalized increase in cellular MMP-2 immunoreactivity at 24-h reperfusion (in neurons, glia and vessels) whereas at 72-h reperfusion the increase in MMP-2 was predominantly in glia. These glial alterations contributed to a significant increase in pro MMP-2 levels in ischemic regions (P < 0.01) as measured by zymography. In contrast, MMP-9 was predominantly upregulated in neurons and this was significantly different to shams at 24- and 72-h reperfusion after ischemia (P < 0.05). Notably, a dramatic increase in proteolytic activity in neurons was observed 24 h after ischemia and this response was absent at 72 h post-ischemia. The present data are supportive of a role for MMPs in contributing to neuronal injury after ischemia.
Division of Neuroscience, University of Edinburgh, Edinburgh EH8 9JZ, UK. smagnoni@policlinico@mi.it
Sandra
S
Magnoni
Andrew
A
Baker
Sarah Jane
SJ
George
W Colin
WC
Duncan
Lorraine E
LE
Kerr
James
J
McCulloch
Karen
K
Horsburgh
D000818:Animals; D001921:Brain / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000201:enzymology* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000473:pathology; D013997:Time Factors; D014018:Tissue Distribution
D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9