Platelet adhesion receptors do not modulate infarct volume after a photochemically induced stroke in mice.
Photochemically induced cerebral infarction has been considered a clinically relevant model for ischemic stroke. We evaluated various transgenic mice to study the role of platelet adhesion molecules in this model. Infarction to the sensorimotoric cortex was induced by erythrosin B and laser light. Infarct volumes were calculated from triphenyltetrazolium chloride stained brain slices. Thrombus formation and vessel leakage were observed in vivo by multiphoton microscopy. Mice mutant in VWF, GPIbalpha, beta3 integrin, and P-selectin did not show any significant differences in infarct volume compared to wild type (WT). This is in contrast to the intraluminal middle cerebral artery occlusion model in which alphaIIbbeta3 integrin, GPIbalpha, and P-selectin are known to modulate infarct size. Multiphoton microscopy showed that small, non-occlusive embolizing platelet thrombi formed in the photochemically injured brains. Massive vessel leakage was observed within 25 min of laser injury. Interestingly, we observed a significant increase in infarct size with aging, accordant with heightened fragility of the blood brain barrier (BBB) in older mice. This model of photochemically induced stroke is closer to a BBB injury model than a thrombotic stroke model in which platelets and their adhesion molecules are crucial. This model will be useful to study mechanisms regulating BBB permeability.
Frederix
Kim
K
Department of Internal Medicine, Laboratory for Clinical Thrombosis and Haemostasis, University Hospital and Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
Chauhan
Anil K
AK
Kisucka
Janka
J
Zhao
Bing-Qiao
BQ
Hoff
Erik I
EI
Spronk
Henri M H
HM
Ten Cate
Hugo
H
Wagner
Denisa D
DD
D000367:Age Factors; D000818:Animals; D000941:Antigens / Q000235:genetics; D020520:Brain Infarction / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D039661:Integrin beta3 / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019007:P-Selectin / Q000235:genetics; D010777:Photochemistry / Q000379:methods*; D011956:Receptors, Cell Surface / Q000172:deficiency; D020521:Stroke / Q000150:complications* / Q000209:etiology*; D013997:Time Factors; D014841:von Willebrand Factor / Q000276:immunology; D053662:Interleukin-4 Receptor alpha Subunit
D000941:Antigens; D015815:Cell Adhesion Molecules; D039661:Integrin beta3; D019007:P-Selectin; D011956:Receptors, Cell Surface; D014841:von Willebrand Factor; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit; C029417:Von Willebrand antigen