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.
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