An experimental study on reversible opening of the blood-brain barrier.

使用荧光素钠作为从血液到脑组织的渗透性的指标，我们先前证明了血脑屏障可能被惊厥性电击打开。在本研究中，我们研究了荧光素标记的不同分子大小的右旋糖酐（FITC-dextrans）对血脑屏障的通透性是否会在最大电击（ES; 50 mA， 0.2秒）或吸入<CO_2>时发生改变。使用雄性成年小鼠。FITC-dextrans于ES前30秒或<CO_2>吸入前（<N_2>:40%, <O_2>: 20%, <CO_2>:40%）注射于尾。给药一分钟后，动物被斩首，大脑被迅速移除。荧光法测定脑内fitc -右旋糖酐含量。大鼠小脑、大脑皮层、脑干、间脑及中脑中分子量为150000的fitc -葡聚糖水平明显升高。吸入<CO_2>时，大鼠全脑fitc -葡聚糖（mol.Wt.= 70000）水平升高，但fitc -葡聚糖（mol.Wt.= 150000）水平不变。ES和<CO_2>吸入也增加了成年小鼠6-羟基多巴胺（6-OHDA）的渗透，因为外周给药显著降低了脑内去甲肾上腺素的含量。地西泮预处理（1- 2mg /kg, ig）以剂量依赖性延长后发昏迷期，而惊厥模式不变。治疗还延长了<CO_2> -诱导的睡眠时间。这些结果表明，吸入ES或<CO_2>可能通过打开血脑屏障而增强地西泮进入大脑的渗透。ES打开血脑屏障的机制被认为是由于大电流对脑血管内皮细胞的功能干扰，和/或由于长时间强直性惊厥引起的低氧血症或高呼吸。

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.