• Journal of Life Science
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• v.17 no.7 s.87
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• pp.1019-1022
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• 2007

Thrombolytic therapy with tissue plasminogen activator (tPA) can improve the clinical outcome of ischemic stroke patients. However, its clinical application is limited by narrow therapeutic time windows and elevated risks of cerebral hemorrhage and brain injury. In part, these effects of tPA has been related to matrix metalloproteinase-9 (MMP-9) dysregulation. Here, we investigate that the effects of alteplase (tPA with short half-life) and pamiteplase (a modified tPA with long half-life) on the MMP-9 regulation in neurovascualr unit. The total levels of MMP-2 and MMP-9 in neuronal cells are lower than astrocytes. Alteplase (1-10 ${\mu}g/ml$) induced upregulation of MMP-2 and MMP-9 in rat cortical neurons and astrocytes, respectively. Whereas pamiteplase in a wide range of dose did not affect the MMP-2 and MMP-9 responses in both of cells. These results suggest that pamiteplase with long half-life can be provided as a agent that overcome the side effects of alteplase.