title: Tissue plasminogen activator mediated blood-brain barrier damage in transient focal cerebral ischemia in rats: relevance of interactions between thrombotic material and thrombolytic agent.
abstract: Thrombolysis with tPA for acute ischemic stroke is associated with an increased risk of intracerebral hemorrhage. We investigated the impact of thrombolysis with tPA on the blood-brain barrier in a suture occlusion model in rats. Cerebral ischemia was performed for 2 h followed by 22 h of reperfusion. Treatment groups received either saline (A), 10 mg/kg bw rtPA (B) or "activated" rtPA (ArtPA, C, rtPA with in vitro clot contact). Blood-brain-barrier damage assessed by Evans blue extravasation as a permeability marker was significantly enhanced in basal ganglia of group C compared to groups A or B. Likewise was the upregulation of MMP-9. Interestingly, results of the rtPA and saline group showed only minor and not statistically significant differences. The results of the present study indicate a major role for thrombus-thrombolytic interaction in focal cerebral ischemia with subsequent increased BBB permeability.
authors.affiliation: Department of Neurology, University Hospital, JW Goethe University Frankfurt, Schleusenweg 2-16, ZNN, 60528 Frankfurt/Main, Germany. t.kahles@em.uni-frankfurt.de
authors.forename: Timo
authors.initials: T
authors.lastname: Kahles
authors.forename: Christian
authors.initials: C
authors.lastname: Foerch
authors.forename: Matthias
authors.initials: M
authors.lastname: Sitzer
authors.forename: Michael
authors.initials: M
authors.lastname: Schroeter
authors.forename: Helmuth
authors.initials: H
authors.lastname: Steinmetz
authors.forename: Abdelhaq
authors.initials: A
authors.lastname: Rami
authors.forename: Tobias
authors.initials: T
authors.lastname: Neumann-Haefelin
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000473:pathology; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000473:pathology; D005070:Evans Blue; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000473:pathology*; D017078:Laser-Doppler Flowmetry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology; D013927:Thrombosis / Q000473:pathology*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
chemical_list: D005343:Fibrinolytic Agents; D005070:Evans Blue; D010959:Tissue Plasminogen Activator; D020780:Matrix Metalloproteinase 9