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

Abstract

BACKGROUND:

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.

METHODOLOGY/PRINCIPAL FINDINGS:

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.

CONCLUSION:

Our study shows that TAFI does not play a major role for thrombus formation and neuronal degeneration after ischemic brain challenge.

• Authors: Peter Kraft, Tobias Schwarz, Joost C M Meijers, Guido Stoll, Christoph Kleinschnitz
• Journal: PloS one (PLoS One) Vol. 5 Issue 7 Pg. e11658 (Jul 19 2010) ISSN: 1932-6203 [Electronic] United States
• PMID: 20657835 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carboxypeptidase B2

Topics

• Animals
• Blotting, Western
• Carboxypeptidase B2 (deficiency, genetics, metabolism)
• Disease Susceptibility
• Intracranial Thrombosis (genetics, pathology)
• Laser-Doppler Flowmetry
• Mice
• Mice, Mutant Strains
• Stroke (genetics, pathology)