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To test this hypothesis, we used intravital 2-photon microscopy to examine leakage of fluorescent dextrans from the vasculature in a rodent model of IRI. Minocycline significantly reduced the extent of dextran (500 kDa) leakage from the renal microvasculature 24 h after ischemia. Although minocycline diminished leukocyte accumulation in the kidney following ischemia, areas of leukocyte accumulation did not correlate with areas of microvascular permeability in either the saline- or minocycline-pretreated animals. Minocycline diminished the perivascular increase in MMP-2 and MMP-9, as well as the increase in MMP-2 activity 24 h after ischemia. ABT-518, a specific inhibitor of MMP-2 and MMP-9, also significantly reduced the extent of dextran (500 kDa) leakage from the renal microvasculature 24 h after ischemia. Our results indicate that minocycline mitigates the renal microvascular permeability defect following IRI. This effect is spatially distinct from the effect of minocycline on leukocyte accumulation and may be related to diminished activity of MMPs on the integrity of the perivascular matrix. <\/jats:p>","DOI":"10.1152\/ajprenal.00051.2004","type":"journal-article","created":{"date-parts":[[2004,9,8]],"date-time":"2004-09-08T01:43:15Z","timestamp":1094607795000},"page":"F91-F97","source":"Crossref","is-referenced-by-count":102,"title":["Minocycline reduces renal microvascular leakage in a rat model of ischemic renal injury"],"prefix":"10.1152","volume":"288","author":[{"given":"Timothy A.","family":"Sutton","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. 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