| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1986: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1985: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
|---|
| Research Abstract |
Using fluorescein sodium as an indicator of the permeability from the blood to the brain tissues, we previously demonstrated that the blood-brain barrier may be opened by convulsive electroshock. In the present study, we investigated whether the permeability of various molecular sizes of dextrans labelled by fluorescein (FITC-dextrans) to the blood-brain barrier would be changed by maximal electroshock (ES; 50 mA, 0.2 sec) or <CO_2> inhalation. Male ddY adult mice were used. FITC-dextrans were injected into the tail vain 30 sec prior to ES or <CO_2> inhalation( <N_2> : 40%, <O_2> : 20%, <CO_2> :40%). One min after administration, animals were decapitated and the brain was quickly removed. FITC-dextrans contents of the brain were determined fluorimetrically. The levels of FITC-dextran with a molecular weight (mol.Wt.) of 150,000 in the cerebellum, cerebral cortex, brainstem and diencephalon plus midbrain were markedly increased by ES. With inhalation of <CO_2> , the whole brain level of FITC-dextran (mol.Wt.=70,000) was increased but the level of FITC-dextran (mol.Wt.=150,000) was unchanged. The ES and <CO_2> inhalation were found to also increase the penetration of 6-hydroxy-dopamine (6-OHDA) in adult mice, since norepinephrine contents of the brain were markedly decreased by peripheral administration. Pretreatment with diazepam (1-2 mg/kg, i.p.) prolonged dose-dependently the postictal coma period, while the pattern of convulsion was unaltered. The treatment also prolonged the <CO_2> -induced sleeping time. These results suggest that ES or <CO_2> inhalation may enhance the penetration of diazepam into the brain by opening the blood-brain barrier. The mechanisms by which the blood-brain barrier is opened by ES were thought to be due to functional disturbance of the endothelial cells of the brain vessels by a large current, and/or due to hypoxemia or hypercapnea induced by prolonged tonic convulsions.
|
