title: Expression and activation of matrix metalloproteinase-2 and -9 in rat brain after transient focal cerebral ischemia.
abstract: Matrix metalloproteinases (MMPs) degrade the extracellular matrix and carry out key functions during development and after injury. By means of zymography, Western blot and immunohistochemistry, we studied MMP-2 (gelatinase A) and MMP-9 (gelatinase B) in rat brain after focal cerebral ischemia. The control 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 to neurons and myelinated fibre tracts. Ischemia greatly increased MMP activation in two temporal waves, in the first one, MMP-9 protein was induced from 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 progressive induction of MMP-9 proform, likely in neurons, shortly after ischemia. For MMP-2, the results suggest a discrete production immediately after reperfusion, while a very enhanced expression and activation of MMP-2 attributable to microglia/macrophages occurs on day 4, and it might contribute to the phagocytic action of these reactive cells.
authors.affiliation: Departament de Farmacologia i Toxicologia, Institut d'Investigacions Biomèdiques de Barcelona, Barcelona, Spain.
authors.forename: A M
authors.initials: AM
authors.lastname: Planas
authors.forename: S
authors.initials: S
authors.lastname: Solé
authors.forename: C
authors.initials: C
authors.lastname: Justicia
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology*; D004730:Endothelium, Vascular / Q000201:enzymology; D004789:Enzyme Activation; D004790:Enzyme Induction; D004792:Enzyme Precursors / Q000378:metabolism; D007124:Immunoenzyme Techniques; D002546:Ischemic Attack, Transient / Q000201:enzymology*; D008264:Macrophages / Q000201:enzymology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009413:Nerve Fibers, Myelinated / Q000201:enzymology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000201:enzymology; D009474:Neurons / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology; D013997:Time Factors
chemical_list: D004792:Enzyme Precursors; D009419:Nerve Tissue Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9