Uchiyama-Tsuyuki Y, Kawashima K, Araki H, Otomo S
Department of Pharmacology, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Pharmacol Biochem Behav. 1995 Nov;52(3):555-9. doi: 10.1016/0091-3057(95)00139-n.
The effects of the stable prostacyclin analogue TTC-909 on memory impairment in the water maze task and on neuronal damage were studied in rats with cerebral embolism induced by injecting polyvinyl acetate (PVA) into the right internal carotid artery and the ensuing embolism extending out into the right middle cerebral artery. Areas supplied by the lenticulostriate artery were most markedly damaged. In the water maze test, the PVA-embolized rats took longer to reach the platform than did the nontreated control rats. To some extent, repeated administrations of TTC-909 (200 ng/kg, IV) overcame this impairment in water maze learning in the rats. We assume that the vasodilating effects of TTC-909 maintain this blood supply to the ischemic area and that TTC-909 prevents the development of thrombosis around the PVA particles in the arterial capillaries, as a result of antiplatelet aggregative effects. These two mechanisms are likely to be involved in memory improvement. TTC-909 may prove effective for treating subjects with stroke and other cerebrovascular disorders.
通过向大鼠右颈内动脉注射聚醋酸乙烯酯（PVA）诱导脑栓塞，随后栓塞延伸至右大脑中动脉，研究了稳定前列环素类似物TTC - 909对水迷宫任务中记忆损伤及神经元损伤的影响。豆纹动脉供血区域受损最为明显。在水迷宫试验中，PVA栓塞大鼠到达平台的时间比未处理的对照大鼠更长。在一定程度上，重复给予TTC - 909（200 ng/kg，静脉注射）可克服大鼠水迷宫学习中的这种损伤。我们推测，TTC - 909的血管舒张作用维持了对缺血区域的血液供应，并且由于其抗血小板聚集作用，TTC - 909可防止动脉毛细血管中PVA颗粒周围血栓形成。这两种机制可能与记忆改善有关。TTC - 909可能被证明对治疗中风和其他脑血管疾病患者有效。
