Activation Systems for Latent Matrix Metalloproteinase-2 Are Upregulated Immediately after Focal Cerebral Ischemia

Dae Il Chang, Naohisa Hosomi, Jacinta Lucero, Ji Hoe Heo, Takeo Abumiya, Andrew P. Mazar, Gregory J. Del Zoppo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

130 Scopus citations


During focal cerebral ischemia, matrix metalloproteinase-2 (MMP-2) can contribute to the loss of microvessel integrity within ischemic regions by degrading the basal lamina. MMP-2 is secreted in latent form (pro-MMP-2), but the activation of pro-MMP-2 in the ischemic territory has not been shown. Immunohistochemical and in situ hybridization studies of the expression of the direct activators of MMP-2, MT1-MMP and MT3-MMP, and the indirect activation system tissue plasminogen activator, urokinase (u-PA), its receptor (u-PAR), and its inhibitor PAI-1 after middle cerebral artery occlusion/reperfusion were undertaken in basal ganglia samples from 26 adolescent male baboons. The expressions of all three MMPs, u-PA, u-PAR, and PAI-1, but not tissue plasminogen activator, were increased from 1 hour after middle cerebral artery occlusion in the ischemic core. mRNA transcripts confirmed the increases in latent MMP-2, u-PA, u-PAR, and PAI-1 antigen very early after middle cerebral artery occlusion. The expression patterns are consistent with secretion of pro-MMP-2 and its activators in the ischemic core, perhaps from separate cell compartments. The rapid and coordinate appearance of pro-MMP-2 and its activation apparatus suggest that in the primate striatum this protease may participate in matrix injury during focal cerebral ischemia.

Original languageEnglish (US)
Pages (from-to)1408-1419
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number12
StatePublished - Dec 2003


  • Focal ischemia
  • Metalloproteinase
  • Microvessel
  • Urokinase
  • u-PAR

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Cardiology and Cardiovascular Medicine


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