Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) Deficient Mice Are Susceptible to Intracerebral Thrombosis and Ischemic Stroke

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 (T...

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Published in:PloS one Vol. 5; no. 7; p. e11658
Main Authors: Kraft, Peter, Schwarz, Tobias, Meijers, Joost C. M., Stoll, Guido, Kleinschnitz, Christoph
Format: Journal Article
Language:English
Published: United States Public Library of Science 19.07.2010
Public Library of Science (PLoS)
Subjects:
Activation
Analysis
Animal models
Animals
Basal ganglia
Binding sites
Blood clots
Blotting, Western
Brain
Brain damage
Brain slice preparation
Carboxypeptidase B2 - deficiency
Carboxypeptidase B2 - genetics
Carboxypeptidase B2 - metabolism
Cardiovascular disease
Cerebral blood flow
Coagulation
Degeneration
Disease Susceptibility
Fibrin
Fibrinolysis
Ganglia
Histology
Inhibitors
Intracranial Thrombosis - genetics
Intracranial Thrombosis - pathology
Ischemia
Laser-Doppler Flowmetry
Mice
Mice, Mutant Strains
Neurodegeneration
Neurological Disorders/Cerebrovascular Disease
Neurological Disorders/Epilepsy
Neurological Disorders/Neuroimaging
Neurology
Neurons
Occlusion
Risk factors
Rodents
Stroke
Stroke - genetics
Stroke - pathology
Studies
Thrombin
Thromboembolism
Thrombosis
Transgenic animals
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary: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 analyzed by immunoblot. Infarct volumes and functional outcomes did not significantly differ between TAFI-/- mice and controls (p>0.05). Histology revealed extensive ischemic neuronal damage regularly including the cortex and the basal ganglia in both groups. TAFI deficiency also had no influence on intracerebral fibrin(ogen) formation after tMCAO. Our study shows that TAFI does not play a major role for thrombus formation and neuronal degeneration after ischemic brain challenge.
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Conceived and designed the experiments: PK CK. Performed the experiments: PK TS. Analyzed the data: PK TS CK. Contributed reagents/materials/analysis tools: JCM. Wrote the paper: PK TS JCM GS CK.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0011658