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dc.contributor.authorMachado, Livia Sampaio
dc.date.accessioned2014-03-04T18:16:01Z
dc.date.available2014-03-04T18:16:01Z
dc.date.issued2009-05
dc.identifier.othermachado_livia_s_200905_phd
dc.identifier.urihttp://purl.galileo.usg.edu/uga_etd/machado_livia_s_200905_phd
dc.identifier.urihttp://hdl.handle.net/10724/25552
dc.description.abstractBACKGROUND: Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) are increased in the brain after experimental ischemic stroke in rats. These two proteases are involved with the degradation of the basal lamina and loss of stability of the blood brain barrier that occurs after ischemia and that is associated with thrombolytic therapy in ischemic stroke. Minocycline is a lipophilic tetracycline and is neuroprotective in several models of brain injury. Minocycline inhibits inflammation, apoptosis and extracellular matrix degradation. In this study we investigated whether delayed minocycline inhibits brain MMPs activated by ischemia in a model of temporary occlusion in Wistar rats. RESULTS: Both MMP-2 and MMP-9 were elevated in the ischemic tissue as compared to the contra-lateral hemisphere after 3 hours occlusion and 21 hours survival (p < 0.0001 for MMP-9). Intraperitoneal minocycline at 45 mg/kg concentration twice a day (first dose immediately after the onset of reperfusion) significantly reduced gelatinolytic activity of ischemia-elevated MMP-2 and MMP-9 (p < 0.0003). Treatment also reduced protein concentration of both enzymes (p < 0.038 for MMP-9 and p < 0.018 for MMP-2). In vitro incubation of minocycline in concentrations as low as 0.1 mug/ml with recombinant MMP-2 and MMP-9 impaired enzymatic activity and MMP-9 was more sensitive at lower minocycline concentrations (p < 0.05). CONCLUSION: Minocycline inhibits enzymatic activity of gelatin proteases activated by ischemia after experimental stroke and is likely to be selective for MMP-9 at low doses. Minocycline is a potential new therapeutic agent to acute treatment of ischemic stroke.
dc.languageeng
dc.publisheruga
dc.rightspublic
dc.subjectminocycline
dc.subjectMMP
dc.subjectstroke
dc.titleMinocycline vascular protection after acute ischemic stroke
dc.typeDissertation
dc.description.degreePhD
dc.description.departmentClinical and Administrative Pharmacy
dc.description.majorPharmacy
dc.description.advisorSusan Fagan
dc.description.committeeSusan Fagan
dc.description.committeeAlvin Terry, Jr.
dc.description.committeeRandall Tackett
dc.description.committeeWilliam Hill
dc.description.committeeAdviye Ergul


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