2003 Fiscal Year Final Research Report Summary
Evaluation of tissue plasminogen activator through the cerebral vessels
| Project/Area Number |
14571338
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Nihon University |
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Principal Investigator |
KANO Tsuneo Nihon University, School of Medicine, Assistant Professor, 医学部, 講師 (40277413)
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| Co-Investigator(Kenkyū-buntansha) |
KATAYAMA Yoichi Nihon University, School of Medicine, Professor, 医学部, 教授 (00125048)
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| Project Period (FY) |
2002 – 2003
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| Keywords | rat / thromboembolic stroke / reperfusion / tissue plasminogen activator / neurotoxicity |
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| Research Abstract |
Object. Recently neurotoxic effects of tissue plasminogen activator (tPA) have been reported. Using a rat model of thromboembolic stroke, we evaluated the extent and degree of extravasation of tPA administered for the purpose of fibrinolysis.
Methods. In a thromboembolic model using Sprague-Dawley rats, focal cerebral ischemia was induced at the territory of the middle cerebral artery (MCA). Early reperfusion was induced by administering tPA (10 mg/kg) intravenously at 30 minutes after the onset of ischemia. Extravasated tPA was evaluated by immunohistochemistry, and the concentration of tPA in the brain tissue was quantified by enzyme-linked immunosorbent assay methods. The integrity of the blood-brain barrier (BBB) was examined electromicroscopically. In a thread model of transient ischemia, reperfusion was induced without tPA administration at 30 minutes or 2 hours after the onset of ischemia and tPA content of the brain was quantified.
Results. In rats with thromboembolic stroke, extravasation of tPA was observed at the territory of the MCA. The tPA contents were significantly higher in the ischemic hemisphere than in the non-ischemic hemisphere : 3.8 and 0.8 ng/mL of the homogenized brain in saline, respectively (p<0.01). Electronmicroscopically, mild ischemic changes were observed, although the integrity of the BBB was preserved. In thread model rats, tPA content of the ischemic hemisphere was significantly lower compared to that of the ischemic hemisphere in the thromboembolic model (p<0.01).
Conclusions. The present findings demonstrate that significant extravasation of tPA occurs through the cerebral vessels even though early reperfusion is induced.
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