Expression and activation of matrix metalloproteinase-2 and-9 in rat brainafter transient focal cerebral ischemia

Matrix metalloproteinases (MMPs) degrade the extracellular matrix and carry out key functions during development and after injury. By means of zymogra phy, Western blot and immunohistochemistry, we studied MMP-2 (gelatinase A) and MMP-9 (gelatinase B) in rat brain after focal cerebral ischemia. The c ontrol rat brain showed constitutive MMP-2 and, to a lesser extent, MMP-9, which were mainly present as prozymogens. MMP-2 protein was located in the cell body of neurons, glia, and endothelium, whereas MMP-9 was associated t o neurons and myelinated fibre tracts. Ischemia greatly increased MMP activ ation in two temporal waves, in the first one, MMP-9 protein was induced fr om 4 h to 4 days, and also a small and short-lasting increase in MMP-2 was detected at 4 h. The second wave showed a massive increase in MMP-2 protein expression and activation by day 4, which was compatible with abundant MMP -2 in reactive microglia/macrophages. Our results are compatible with progr essive induction of MMP-9 proform, likely in neurons, shortly after ischemi a. For MMP-2, the results suggest a discrete production immediately after r eperfusion, while a very enhanced expression and activation of MMP-2 attrib utable to microglia/macrophages occurs on day 4, and it might contribute to the phagocytic action of these reactive cells. (C) 2001 Academic Press.