Lack of TAFI increases brain damage and microparticle generation after thrombolytic therapy in ischemic stroke. Issue 2 (August 2015)

• Record Type: Journal Article
• Authors: Orbe, J.; Alexandru, N.; Roncal, C.; Belzunce, M.; Bibiot, P.; Rodriguez, J.A.; Meijers, J.C.M.; Georgescu, A.; Paramo, J.A.
• Is Part Of: Thrombosis research. Volume 136:Issue 2(2015)
• Page Start: 445
• Page End: 450
• Publication Date: 2015-08
• Subjects: Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2015.06.010
• Languages: English
• ISSNs: 0049-3848

Abstract

<abstract abstract-type="author" id="ab0005"> <title id="st0005">Abstract</title> <sec> <title id="st0010">Background</title> <p id="sp0005">Thrombin-activatable fibrinolysis inhibitor (TAFI) plays an important role in coagulation and fibrinolysis. Whereas TAFI deficiency may lead to a haemorrhagic tendency, data from TAFI knockout mice (TAFI −/−) are controversial and no differences have been reported in these animals after ischemic stroke. There are also no data regarding the role of circulating microparticles (MPs) in TAFI −/−.</p> </sec> <sec> <title id="st0015">Objectives</title> <p id="sp0010">to examine the effect of tPA on the rate of intracranial haemorrhage (ICH) and on MPs generated in a model of ischemic stroke in TAFI −/− mice.</p> </sec> <sec> <title id="st0020">Methods</title> <p id="sp0015">Thrombin was injected into the middle cerebral artery (MCA) to analyse the effect of tPA (10 mg/Kg) on the infarct size and haemorrhage in the absence of TAFI. Immunofluorescence for Fluoro-Jade C was performed on frozen brain slides to analyse neuronal degeneration after ischemia. MPs were isolated from mouse blood and their concentrations calculated by flow cytometry.</p> </sec> <sec> <title id="st0025">Results</title> <p id="sp0020">Compared with saline, tPA significantly increased the infarct size in TAFI −/− mice (p < 0.05). Although plasma fibrinolytic activity (fibrin plate assay) was higher in these animals, no macroscopic or microscopic ICH was detected. A positive signal for apoptosis and degenerating neurons was observed in the infarct area, being significantly higher in tPA treated TAFI −/− mice (p < 0.05). Interestingly, higher numbers of MPs were found in TAFI −/− plasma as compared to wild type, after stroke (p < 0.05).</p> </sec> <sec> <title id="st0030">Conclusions</title> <p id="sp0025">TAFI deficiency results in increased brain damage in a model of thrombolysis after ischemic stroke, which was not associated with bleeding but with neuronal degeneration and MP production.</p> </sec> </abstract>