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Changes in local cerebral glucose utilization (LCGU) of the postischemic rat brain were investigated using the rat four-vessel occlusion model. Following 20 or 30 min of ischemia, LCGUs of the cerebral cortices, striatum and hippocampus were decreased at 1 and 3 days postischemia, but were recovered at 7 days postischemia. Effects of repeated administration of RS-8359, (±)-4-(4-cyanoanilino)-7-hydroxycyclopenta(3,2-e)pyrimidine, (30 mg/kg×2/day, p.o., 4 days) were examined at 3 days postischemia following 20 min of ischemia. Compared with the sham-operated group, the LCGUs of 22 out of 34 structures examined in the ischemic-control group were significantly reduced. In the RS-8359-treated group, however, significant reduction was observed in only 9 structures. Compared with the ischemic-control group, RS-8359 significantly ameliorated the reduction of LCGU in 12 structures. These results suggest that RS-8359 has beneficial effects on reduced glucose metabolism in the postischemic brain.

Single and repeated administration studies of bromodichloromethane(BDCM) were carried out in wistar rats given this gavage as an olive oil solution and by microcapsule. BDCM dissolved in olive oil or enmicrocapsulated was administered once to each group of 3 rats at a dose of 20mg/animal. A continuing high concentration of BDCM was noted in the microcapsules group. The groups of 10 male wistar rats were fed a diet containing 0, 0.024, 0.072 and 0.215% of BDCM, encapsulated, ad lib. (feed group). The groups of 10 male rats were administered at doses of 0, 20, 60 and 180mg/kg of BDCM in 10% olive oil, once a day by stomach tube (gavage group), comparable with the feed group, for a month. The depression of body weight gain at the high dose level of the feed group was observed markedly throughout the administration period. At the high dose of the gavage group, on the other hand, was noted a slight depression at an early stage and became gradually more depressed. The absolute weights of most organs decreased at the high dose of the feed group. On the contraray, the relative weights of liver and kidneys increased at the high dose of the gavage group. Decreases of GLU, T-GLY and ChE activities were revealed at the high dose of the feed group and at the middle and high doses of the gavage group. The degree of liver fatty degeneration was mild in the feed group compared to the gavage group, and degree of hepatocyte necrosis was mild in the gavage group.

In order to know acute toxicities of environmental pollutants and drugs on human brain, mammalian brain slices have been proposed as a suitable assay system(1). Clioquinol is known to cause a subacute myelo-optico neuropathy (SMON). Clioquinol and related compounds; 5-chloro,7-iodo, 8-hydroxyquinoline(CI·I-HQ), 5,7-dichloro,8-hydroxyquinoline(Cl·Cl·HQ), 5-chloro,8-hydroxyquinoline (Cl·HQ), 8-hydroxyquinoline(HQ), 8-hydroxyquinoline, 5-sulfonic acid(HQ-S) were applied to the guinea pig olfactory cortex slices in vitro ,and amplitudes of the postsynaptic potentials evoked by the electrical stimulation of lateral clfactory tracts were observed. These compounds inhibited the synaptic transmission in the slices at the concentration of 100 μM. Percent inhibitions at 20 min after the additions were: Cl-I-HQ,40%; Cl·Cl·HQ,38 % ; Cl·HQ,35%; HQ,25%; HQ-S,14%. To test chronic toxicities, they were added to cell cultures of neuroblastoma originated from rat brain. Cl-I-HQ and C1-C1-HQ (each 100 pM) did not change the viability and morphology until 1 hr after the addition. The result suggests that the acute toxicity of clioquinol and related compounds on the synaptic transmission in brain slices does not come from their cyto-toxicity.