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通透性的指示剂，我们先前证明了惊厥性电击可以打开血脑屏障。在本研究中，我们研究了不同分子大小的荧光素标记的葡聚糖对血脑屏障的通透性是否会因最大电击(Es；50 mA，0.2秒)或吸入CO_2而改变。选用雄性Ddy成年小鼠。在ES或&lt；CO_2&gt；吸入前30秒将FITC-葡聚糖注入尾静脉(&lt；N_2&gt；：40%，&lt；O_2&gt；：20%，&lt；CO_2&gt；：40%)。给药一分钟后，动物被斩首，并迅速取出大脑。荧光法测定脑组织FITC-葡萄糖反式转运体含量。FITC-葡聚糖的相对分子质量(摩尔重量)在150,000个小脑中，大脑皮层、脑干和间脑+中脑明显增加。吸入~lt；CO_2&Gt；后，全脑FITC-葡聚糖(摩尔重量=70,000)水平升高，而FITC-葡聚糖(摩尔重量=150,000)水平无明显变化。吸入ES和~lt；CO_2&Gt；也能增加6-羟基多巴胺(6-OHDA)在成年小鼠体内的渗透率，因为外周给药可显著降低脑内去甲肾上腺素的含量。静脉注射安定(1-2 mg/kg，i.p)。剂量依赖性地延长了昏迷期，而惊厥模式没有改变。治疗还能延长~lt；CO_2&gt；诱导的小鼠睡眠时间。这些结果提示，ES或&lt；CO_2&gt；吸入剂可能通过开放血脑屏障而增强安定的脑渗透。ES开放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障碍，和/或由于长时间的强直性惊厥引起的低氧血症或高碳酸血症。

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.