dc.contributor.author | Gursoy-Ozdemir, Y | |
dc.contributor.author | Can, A | |
dc.contributor.author | Dalkara, T | |
dc.date.accessioned | 2019-12-10T11:25:54Z | |
dc.date.available | 2019-12-10T11:25:54Z | |
dc.date.issued | 2004 | |
dc.identifier.issn | 0039-2499 | |
dc.identifier.uri | https://doi.org/10.1161/01.STR.0000126044.83777.f4 | |
dc.identifier.uri | http://hdl.handle.net/11655/15731 | |
dc.description.abstract | Background and Purpose-Use of thrombolysis in stroke is limited by a short therapeutic window because delayed reperfusion may cause brain hemorrhage and edema. Available evidence suggests a role for superoxide, NO, and peroxynitrite in reperfusion-induced injury. However, depending on their cellular origin and interactions between them, these molecules may exert protective or deleterious actions, neither of which is characterized in the intact brain. Methods-Using fluorescent probes, we determined superoxide and peroxynitrite formation within neurons, astrocytes, and endothelium, and the association between oxidative/nitrative stress and vascular injury in mice brains subjected to 2-hour middle cerebral artery occlusion and 3 or 5 hours of reperfusion. Results-Both signals were colocalized, suggesting that the main source of peroxynitrite in the reperfused brain was a reaction between superoxide and NO. Superoxide and peroxynitrite formation was particularly intense in microvessels and astrocytic end-feet surrounding them, and overlapped with dense mitochondrial labeling. Sites of oxidative/nitrative stress on microvessels were colocalized with markers of vascular injury such as Evans blue (EB) leakage and matrix metalloproteinase-9 (MMP-9) expression, suggesting an association between peroxynitrite and microvascular injury. Supporting this idea, partial inhibition of endothelial NO synthesis at reperfusion with a low dose of L-nitroarginine (1 mg/kg IP) reduced 3-nitrotyrosine formation in microvessels and EB extravasation. Conclusion-During reperfusion, intense superoxide, NO, and peroxynitrite formation on microvessels and surrounding end-feet may lead to cerebral hemorrhage and edema by disrupting microvascular integrity. Combination of thrombolysis with agents diminishing oxidative/nitrative stress may reduce reperfusion-induced injury and extend the therapeutic window for thrombolysis. | |
dc.language.iso | en | |
dc.publisher | Lippincott Williams & Wilkins | |
dc.relation.isversionof | 10.1161/01.STR.0000126044.83777.f4 | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | Neurosciences & Neurology | |
dc.subject | Cardiovascular System & Cardiology | |
dc.title | Reperfusion-Induced Oxidative/Nitrative Injury To Neurovascular Unit After Focal Cerebral Ischemia | |
dc.type | info:eu-repo/semantics/article | |
dc.type | info:eu-repo/semantics/publishedVersion | |
dc.relation.journal | Stroke | |
dc.contributor.department | Nöroloji | |
dc.identifier.volume | 35 | |
dc.identifier.issue | 6 | |
dc.identifier.startpage | 1449 | |
dc.identifier.endpage | 1453 | |
dc.description.index | WoS | |
dc.description.index | Scopus | |