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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Vydané v:	PloS one Ročník 5; číslo 7; s. e11658
Hlavní autori:	Kraft, Peter, Schwarz, Tobias, Meijers, Joost C. M., Stoll, Guido, Kleinschnitz, Christoph
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Public Library of Science 19.07.2010 Public Library of Science (PLoS)
Predmet:	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
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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 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