新しい脳虚血モデルによる治療薬の薬理作用とメカニズム解明

抄録

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)-(-)-5methyl-1-nicotinoyl-2-pyrazoline), a glutamate release inhibitor and YM90K [6-(1 H-imidazol-lyl)-7-nitro-2, 3(1H, 4H)-qunoxalinedione monohydrochloride], an α -amino-3hydroxy-5methyl-4isoxazole (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.