Tissue plasminogen activator mediated blood-brain barrier damage in transient focal cerebral ischemia in rats: relevance of interactions between thrombotic material and thrombolytic agent.
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.
Kahles
Timo
T
Department of Neurology, University Hospital, JW Goethe University Frankfurt, Schleusenweg 2-16, ZNN, 60528 Frankfurt/Main, Germany. t.kahles@em.uni-frankfurt.de
Foerch
Christian
C
Sitzer
Matthias
M
Schroeter
Michael
M
Steinmetz
Helmuth
H
Rami
Abdelhaq
A
Neumann-Haefelin
Tobias
T
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*
D005343:Fibrinolytic Agents; D005070:Evans Blue; D010959:Tissue Plasminogen Activator; D020780:Matrix Metalloproteinase 9