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.