Blocking of platelets or intrinsic coagulation pathway-driven thrombosis does not prevent cerebral infarctions induced by photothrombosis
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Blocking of platelets or intrinsic coagulation pathway-driven thrombosis does not prevent cerebral infarctions induced by photothrombosis. / Kleinschnitz, Christoph; Braeuninger, Stefan; Pham, Mirko; Austinat, Madeleine; Nölte, Ingo; Renné, Thomas; Nieswandt, Bernhard; Bendszus, Martin; Stoll, Guido.
in: STROKE, Jahrgang 39, Nr. 4, 01.04.2008, S. 1262-8.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Blocking of platelets or intrinsic coagulation pathway-driven thrombosis does not prevent cerebral infarctions induced by photothrombosis
AU - Kleinschnitz, Christoph
AU - Braeuninger, Stefan
AU - Pham, Mirko
AU - Austinat, Madeleine
AU - Nölte, Ingo
AU - Renné, Thomas
AU - Nieswandt, Bernhard
AU - Bendszus, Martin
AU - Stoll, Guido
PY - 2008/4/1
Y1 - 2008/4/1
N2 - BACKGROUND AND PURPOSE: 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.
AB - BACKGROUND AND PURPOSE: 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.
KW - Animals
KW - Antibodies
KW - Anticoagulants
KW - Blood Coagulation
KW - Blood Platelets
KW - Cerebral Hemorrhage
KW - Cerebral Infarction
KW - Factor X
KW - Factor XII
KW - Fluorescent Dyes
KW - Heparin
KW - Immunoglobulin Fab Fragments
KW - Intracranial Thrombosis
KW - Male
KW - Mice
KW - Mice, Mutant Strains
KW - Microscopy, Electron, Transmission
KW - Photochemistry
KW - Platelet Aggregation
KW - Platelet Glycoprotein GPIIb-IIIa Complex
KW - Platelet Glycoprotein GPIb-IX Complex
KW - Rose Bengal
KW - Thrombocytopenia
U2 - 10.1161/STROKEAHA.107.496448
DO - 10.1161/STROKEAHA.107.496448
M3 - SCORING: Journal article
C2 - 18292385
VL - 39
SP - 1262
EP - 1268
JO - STROKE
JF - STROKE
SN - 0039-2499
IS - 4
ER -
