[A novel photochemical model of the middle cerebral artery for thrombosis research and evaluation of anti-thrombotic agents].
We have established a novel thrombosis model of the middle cerebral artery (MCA). The thrombotic occlusion of the MCA was induced by the photochemical reaction between Rose Bengal and green light, which causes endothelial injury followed by platelet adhesion, aggregation and formation of a platelet and fibrin-rich thrombus at the site of the photochemical reaction. With this model, we have investigated the effects of anti-thrombotic agents, thrombolytic agents and neuroprotective agents. In our model, ADP, thromboxane A2 (TXA2) and thrombin play a key role in thrombus formation of the MCA. Tissue-type plasminogen activator (tPA) could cause an opening of the thrombotic MCA occlusion and reduced the size of the cerebral infarction. Furthermore, a TXA2 antagonist enhanced the thrombolytic efficacy of tPA. MS-153 ((R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline), a glutamate release inhibitor and YM90K [6-(1 H-imidazol-1-yl)-7-nitro-2,3(1H, 4H)-qunoxalinedione monohydrochloride, an alpha-amino-3hydroxy-5methyl-4-isoxazole (AMPA) antagonist reduced the cerebral infarction 24 hr after the MCA occlusion. This model is very useful for investigating the mechanisms of anti-thrombotic and neuroprotective agents and evaluating the effects of these agents.
Umemura
K
K
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
D000818:Animals; D004195:Disease Models, Animal; D004341:Drug Evaluation; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005456:Fluorescent Dyes; D018698:Glutamic Acid / Q000378:metabolism; D002542:Intracranial Embolism and Thrombosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008027:Light; D008279:Magnetic Resonance Imaging; D009539:Nicotinic Acids / Q000494:pharmacology / Q000627:therapeutic use; D010777:Photochemistry; D011810:Quinoxalines / Q000494:pharmacology / Q000627:therapeutic use; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012395:Rose Bengal
C101692:5-methyl-1-nicotinoyl-2-pyrazoline; D005343:Fibrinolytic Agents; D005456:Fluorescent Dyes; D009539:Nicotinic Acids; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C086162:6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione; D012395:Rose Bengal; D018698:Glutamic Acid