title: Blocking of platelets or intrinsic coagulation pathway-driven thrombosis does not prevent cerebral infarctions induced by photothrombosis.
abstract: 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.
authors.affiliation: Department of Neurology, University of Würzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kleinschnitz
authors.forename: Stefan
authors.initials: S
authors.lastname: Braeuninger
authors.forename: Mirko
authors.initials: M
authors.lastname: Pham
authors.forename: Madeleine
authors.initials: M
authors.lastname: Austinat
authors.forename: Ingo
authors.initials: I
authors.lastname: Nölte
authors.forename: Thomas
authors.initials: T
authors.lastname: Renné
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
authors.forename: Martin
authors.initials: M
authors.lastname: Bendszus
authors.forename: Guido
authors.initials: G
authors.lastname: Stoll
mesh_terms: 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
chemical_list: 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