Thrombin-activatable fibrinolysis inhibitor (TAFI) deficient mice are susceptible to intracerebral thrombosis and ischemic stroke.

PloS One
Peter KraftChristoph Kleinschnitz

Abstract

Thrombus formation is a key step in the pathophysiology of acute ischemic stroke and results from the activation of the coagulation cascade. Thrombin plays a central role in this coagulation system and contributes to thrombus stability via activation of thrombin-activatable fibrinolysis inhibitor (TAFIa). TAFIa counteracts endogenous fibrinolysis at different stages and elevated TAFI levels are a risk factor for thrombotic events including ischemic stroke. Although substantial in vitro data on the influence of TAFI on the coagulation-fibrinolysis-system exist, investigations on the consequences of TAFI inhibition in animal models of cerebral ischemia are still lacking. In the present study we analyzed stroke development and post stroke functional outcome in TAFI-/- mice. TAFI-/- mice and wild-type controls were subjected to 60 min transient middle cerebral artery occlusion (tMCAO) using the intraluminal filament method. After 24 hours, functional outcome scores were assessed and infarct volumes were measured from 2,3,5-Triphenyltetrazoliumchloride (TTC)-stained brain slices. Hematoxylin and eosin (H&E) staining was used to estimate the extent of neuronal cell damage. Thrombus formation within the infarcted brain areas was analy...Continue Reading

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Citations

Dec 25, 2012·Acta neurologica Belgica·Serhat TokgozAlper Sinan
Jul 26, 2012·Journal of Medicinal Chemistry·Jing WuYihua Zhang
Jun 4, 2013·Lancet Neurology·José Álvarez-SabínCarlos S Kase
Sep 14, 2013·Stroke; a Journal of Cerebral Circulation·Peter KraftChristoph Kleinschnitz
Jul 30, 2016·Stroke; a Journal of Cerebral Circulation·Frederik DenormeSimon F De Meyer
Jun 30, 2012·Stroke; a Journal of Cerebral Circulation·Nadine HeydenreichChristoph Kleinschnitz
Sep 2, 2020·Journal of Thrombosis and Haemostasis : JTH·Joachim C MertensJean-Philippe Desilles
Nov 23, 2019·Journal of Asian Natural Products Research·Xin FangShuang Liang
Jan 23, 2021·International Journal of Molecular Sciences·Karen ClaesenDirk Hendriks

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Methods Mentioned

BETA
protein assay

Software Mentioned

GraphPad Stat Mate
PrismGraph
GraphPad

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