[Effect of bifemelane hydrochloride in rats on the improvement of the learning and memory impairments and prevention of neuronal damage following transient forebrain ischemia].
Modified four-vessel occlusion in rats caused loss of the passive avoidance response (PAR) and impaired the radial maze performance (RMP). We investigated the effectiveness of bifemelane hydrochloride (bifemelane) in restoring these abilities. After the RMP test, the hippocampal neuronal density following cerebral ischemia was observed histologically and the effect of bifemelane on it examined. Bifemelane was intraperitoneally administered at a dose of 1, 3, 10 mg/kg or 30 mg/kg twice before ischemia and daily following cerebral ischemia. The control rats were given physiological saline in the same manner. At a dose of 10 mg/kg, i.p., bifemelane significantly restored the PAR, which had been lost as a result of 5-min ischemia. At the same dose, it significantly restored the RMP, which had been impaired by 15-min ischemia and prevented neuronal damage in the CA2 region of the anterior hippocampus and the CA1, CA2 and CA3 regions of the posterior hippocampus. The correlation between the memory score and the neuronal density in the CA1 region of the posterior hippocampus was statistically significant. These results suggest that bifemelane might prevent the neuronal damage induced by ischemia and restore impaired learning and memory capabilities following cerebrovascular disease.
Department of Drug Research II, Eisai Co., Ltd., Tokyo, Japan.
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S
Ozaki
I
I
Ohkawa
T
T
Nakamura
T
T
Tajima
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001559:Benzhydryl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D002545:Brain Ischemia / Q000473:pathology / Q000523:psychology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008568:Memory / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D001559:Benzhydryl Compounds; C031906:bifemelane