Evaluation of the disintegrin, triflavin, in a rat middle cerebral artery thrombosis model.
Platelet aggregation plays a important role in the thrombotic cerebral infarction. The final common mechanism in the formation of a platelet aggregate is the linking of adjacent platelets by fibrinogen binding to the platelet integrin alpha 11b beta 3. In this study, we evaluated the effect of the disintegrin, triflavin, in a rat middle cerebral artery thrombosis model. Thrombus at the left middle cerebral artery in rat was induced by photochemical reaction between rose bengal and green light, which caused endothelial injury at the site of irradiation. We measured the time to occlusive thrombus formation and the size of ischaemic cerebral damage. Triflavin dose dependently prolonged the time to occlusive thrombus formation in this model. Triflavin also reduced the size of ischaemic cerebral damage on examination at 24 h after photochemical reaction. Triflavin dose dependently inhibited ADP- and collagen-induced platelet aggregation and platelet retention in the collagen-coated beads method ex vivo. These effects were thought to result from the blockade of platelet integrin alpha IIb beta 3. Blockade of platelet integrin alpha IIb beta 3 may be useful in the prevention of cerebral arterial thrombosis.
Kaku
S
S
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Umemura
K
K
Mizuno
A
A
Kawasaki
T
T
Nakashima
M
M
D000818:Animals; D002545:Brain Ischemia / Q000097:blood / Q000517:prevention & control; D002544:Cerebral Infarction / Q000097:blood / Q000517:prevention & control; D003435:Crotalid Venoms / Q000494:pharmacology*; D002542:Intracranial Embolism and Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar
D003435:Crotalid Venoms; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C070025:triflavin