Lack of TAFI increases brain damage and microparticle generation after thrombolytic therapy in ischemic stroke.
Thromb Res
; 136(2): 445-50, 2015 Aug.
Article
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| MEDLINE
| ID: mdl-26118976
ABSTRACT
BACKGROUND:
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-/-.OBJECTIVES:
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.METHODS:
Thrombin was injected into the middle cerebral artery (MCA) to analyse the effect of tPA (10mg/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.RESULTS:
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).CONCLUSIONS:
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.Palabras clave
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Bases de datos:
MEDLINE
Asunto principal:
Activador de Tejido Plasminógeno
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Accidente Cerebrovascular
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Hemorragias Intracraneales
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Carboxipeptidasa B2
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Micropartículas Derivadas de Células
Límite:
Animals
Idioma:
En
Revista:
Thromb Res
Año:
2015
Tipo del documento:
Article