Blocking of platelets or intrinsic coagulation pathway-driven thrombosis does not prevent cerebral infarctions induced by photothrombosis.
OBJECTIVE
Models of photochemically-induced thrombosis are widely used in cerebrovascular research. Photothrombotic brain infarctions can be induced by systemic application of photosensitizing dyes followed by focal illumination of the cerebral cortex. Although the ensuing activation of platelets is well established, their contribution for thrombosis and tissue damage has not formally been proved.


METHODS
Infarction to the cerebral cortex was induced in mice by Rose Bengal and a cold light source. To assess the functional role of platelets, animals were platelet-depleted by anti-GPIbalpha antibodies or treated with GPIIb/IIIa-blocking F(ab)(2) fragments. The significance of the plasmatic coagulation cascade was determined by using blood coagulation factor XII (FXII)-deficient mice or heparin. Infarct development and infarct volumes were determined by serial MRI and conventional and electron microscopy.


RESULTS
There was no difference in development and final size of photothrombotic infarctions in mice with impaired platelet function. Moreover, deficiency of FXII, which initiates the intrinsic pathway of coagulation and is essential for thrombus formation, or blockade of FXa, the key protease during the waterfall cascade of plasmatic coagulation, by heparin likewise did not affect lesion development.


CONCLUSIONS
Our data demonstrate that platelet activation, factor XII-driven thrombus formation, and plasmatic coagulation pathways downstream of FX are not a prerequisite for ensuing tissue damage in models of photothrombotic vessel injury indicating that other pathomechanisms are involved. We suggest that this widely used model does not depend on platelet- or plasmatic coagulation-derived thrombosis.
Kleinschnitz
Christoph
C
Department of Neurology, University of Würzburg, Germany.
Braeuninger
Stefan
S
Pham
Mirko
M
Austinat
Madeleine
M
Nölte
Ingo
I
Renné
Thomas
T
Nieswandt
Bernhard
B
Bendszus
Martin
M
Stoll
Guido
G
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000925:Anticoagulants / Q000494:pharmacology; D001777:Blood Coagulation / Q000502:physiology*; D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure; D002543:Cerebral Hemorrhage / Q000378:metabolism; D002544:Cerebral Infarction / Q000378:metabolism* / Q000517:prevention & control*; D005170:Factor X / Q000037:antagonists & inhibitors / Q000378:metabolism; D005174:Factor XII / Q000235:genetics / Q000378:metabolism; D005456:Fluorescent Dyes / Q000633:toxicity; D006493:Heparin / Q000494:pharmacology; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D020767:Intracranial Thrombosis / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D046529:Microscopy, Electron, Transmission; D010777:Photochemistry; D010974:Platelet Aggregation / Q000502:physiology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000276:immunology; D012395:Rose Bengal / Q000633:toxicity; D013921:Thrombocytopenia / Q000378:metabolism
D000906:Antibodies; D000925:Anticoagulants; D005456:Fluorescent Dyes; D007140:Immunoglobulin Fab Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D012395:Rose Bengal; D005170:Factor X; D005174:Factor XII; D006493:Heparin