Yamazaki N, Kiyota Y, Take Y, Miyamoto M, Nagawa Y, Nagaoka A
Central Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
Arch Gerontol Geriatr. 1989 May;8(3):213-24. doi: 10.1016/0167-4943(89)90004-6.
Two rat models of memory impairment in passive avoidance learning induced by cerebrovascular disturbance, were established to estimate the effects of a cerebral metabolic enhancer, idebenone. Transient and global cerebral ischemia in rats, produced by 4-vessel occlusion for 200 s immediately after the acquisition trial of passive avoidance learning, shortened the latencies in the retention test trial performed 24 h later. This retrograde amnesia was reversed significantly by idebenone administered orally or intraperitoneally at the doses of 10 and 30 mg/kg before the retention test trial. Idebenone at a dose of 10 mg/kg, given intraperitoneally before or immediately after the ischemia, also markedly inhibited the appearance of amnesia. In the second model, permanent and cerebral hemisphere embolization produced by injecting 2,000 microspheres into the internal carotid artery, significantly impaired passive avoidance learning performed 7 days later. The repeated administration of idebenone (30 mg/kg, i.p.). once a day after the embolization, significantly improved the impairment of passive avoidance learning in the embolized rats. Furthermore, physostigmine and arginine-vasopressin as reference compounds improved the impairment of passive avoidance learning in these models. These findings suggest that idebenone ameliorates memory impairment induced by cerebral vascular disturbance in rats.
为评估脑代谢增强剂艾地苯醌的作用，建立了两种由脑血管紊乱诱导的被动回避学习记忆障碍大鼠模型。在被动回避学习获得性试验后立即通过四动脉闭塞200秒造成大鼠短暂性全脑缺血，这缩短了24小时后进行的记忆测试试验中的潜伏期。在记忆测试试验前口服或腹腔注射10和30毫克/千克剂量的艾地苯醌可显著逆转这种逆行性遗忘。在缺血前或缺血后立即腹腔注射10毫克/千克剂量的艾地苯醌也明显抑制了遗忘的出现。在第二个模型中，通过向颈内动脉注射2000个微球造成永久性脑半球栓塞，显著损害了7天后进行的被动回避学习。栓塞后每天一次重复腹腔注射艾地苯醌（30毫克/千克）可显著改善栓塞大鼠被动回避学习的损伤。此外，作为参考化合物的毒扁豆碱和精氨酸加压素改善了这些模型中被动回避学习的损伤。这些发现表明，艾地苯醌可改善大鼠脑血管紊乱诱导的记忆障碍。
