Effects of idebenone on memory impairment induced in ischemic and embolization models of cerebrovascular disturbance in rats.

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.