|Budget Amount *help
¥2,300,000 (Direct Cost : ¥2,300,000)
Fiscal Year 1995 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1994 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1993 : ¥700,000 (Direct Cost : ¥700,000)
This study was designed to elucidate pathophysiological alterations of microsphere-embolized rats, which may mimic multi-infarct dementia. Microspheres (48mum in diameter) were injected to the right internal carotid artery and the animals with stroke-like symptoms were used for the study. Microsphere embolism induced a decrease in blood flow of regional brains including the cerebral cortex, striatum and hippocampus of the animals. In association with this alteration, we observed the decrease in acetylcholine, amino acid, and monoamines such as norepinephrine, dopamine and serotonin of the three brain regions of the microsphere-embolized rats. Histological study also showed a decrease in the length of choline-acetyl transferase-containing fibers, but not the number of cell body. Learning task of the microsphere-embolized animal was examined using passive and active avoidance, and water maze tests, and found to be severely impaired. These results suggest that microsphere-embolized rats induce multi-infarct dementia-like symptoms. The effects of naftidrofuryl oxalate, a cerebral vasodilator, on the pathophysiological alterations of the microsphere-embolized rats were examined. Several improvements such as the reduction in the cortical cerebral blood flow and the partial reverse in acetylcholine, dopamine and serotonin contents, were detected. The results suggest that this model is useful for evaluation of agents which might be beneficial for multi-infarct-induced failure in learning task in animals.