Inhibitory Effect of Clopidogrel, Vapiprost and Argatroban on the Middle Cerebral Artery Thrombosis in the Rat

Abstract

ABSTRACT-This study investigated the roles of thromboxane A2 (TXA2), ADP and thrombin in middle cerebral artery (MCA) thrombosis in the rat. The rat MCA was occluded by a thrombus induced by the photochemical reaction of rose bengal by green light that causes endothelial damage followed by platelet adhesion, aggregation and formation of a platelet and fibrin-rich thrombus at the site of the photochemical reaction. Vapiprost, a specific TXA2-receptor antagonist; clopidogrel, which has the thienopyridine structure of ticlopidine and is a more potent inhibitor of ADP-induced platelet aggregation than ticlopidine; argatroban, a specific thrombin inhibitor; or heparin was administered intravenously before rose bengal injection. The MCA local blood flow was monitored by a laser Doppler flowmeter. The MCA was occluded by thrombus about 5 min after the initiation of the photochemical reaction. Vapiprost, clopidogrel and argatroban all significantly prolonged the time taken for the thrombotic occlusion of the MCA, but in this respect, heparin was ineffective. Our observations suggest that vapiprost and clopidogrel are useful antithrombotic agents against platelet and fibrin-rich thrombi. The effect of argatroban is attributable to inhibition of thrombin-induced platelet activation and fibrin generation. The thrombosis model described in this study is useful for understanding the mechanism(s) of thrombogenesis in the rat MCA and may be applied to other mammalian species.

Human Group IIA Secretory Phospholipase A2Induces Neuronal Cell Death via Apoptosis

“…On the other hand, according to Li et al (1995), in the penumbra around the core, cell death was induced via apoptosis and necrosis. Focal cerebral ischemia was caused in the rat by PIT-MCA occlusion (Umemura et al, 1995). After occlusion, sPLA 2 activity was significantly increased in the cortex, in which the ischemic core and the penumbra coexist.…”

“…Occlusion of the photochemically induced thrombotic (PIT) MCA was performed according to the method of Umemura et al (1995). A catheter for administration of rose bengal was placed in the femoral vein.…”

“…At the beginning of the stroke, there is a definite gradation of injury, a central area or core, with low blood flow already showing signs of massive cell death and an outer area, the penumbra, that is still alive but will malfunction after several days. A rat with the middle cerebral artery (MCA) occluded has been established as an animal model for stroke (Umemura et al, 1995). MCA occlusion causes irreversible necrosis and infarction in the core (Hallenbeck, 1994).…”

Effects of Clopidogrel on Platelet Activation and Coagulation of Non-Anticoagulated Rat Blood under High Shear Stress

“…Platelet aggregation studies performed in vitro and in vivo have shown that ADP is an important agonist in platelet-rich thrombus formation [29][30][31][32][33][34][35]. Ticlopidine and clopidogrel specifically inhibit ADP-induced platelet aggregation [9,10,36,37].…”

Human group IIA secretory phospholipase A2 potentiates Ca2+ influx through L‐type voltage‐sensitive Ca2+ channels in cultured rat cortical neurons

“…Recently, we have found that sPLA 2 -IIA activity in the cerebral cortex was increased after ischemia, and was significantly suppressed by a potent sPLA 2 -specific inhibitor, indoxam (Yagami et al 2002a). Indoxam prevented the neurodegeneration in the penumbra after ischemia, in which apoptosis is caused (Umemura et al 1995). sPLA 2 -IIA caused cell death in primary cultures of rat cortical neurons.…”