Differential alterations in the expression and activity of matrix metalloproteinases 2 and 9 after transient cerebral ischemia in mice

Sandra Magnoni, Andrew Baker, Sarah Jane George, W. Colin Duncan, Lorraine E. Kerr, James McCulloch, Karen Horsburgh

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)188-197
Number of pages10
JournalNeurobiology of Disease
Volume17
Issue number2
DOIs
Publication statusPublished - Nov 2004

Keywords

  • Cerebral ischemia
  • Matrix metalloproteinases (MMPs)
  • Mice
  • Proteolytic activity

ASJC Scopus subject areas

  • Neurology

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