Stewart P A, Hayakawa E M, Carlen P L
Department of Anatomy, University of Toronto, Ont., Canada.
Brain Res. 1988 Mar 8;443(1-2):12-20. doi: 10.1016/0006-8993(88)91593-4.
The structure and function of the blood-brain barrier (BBB) is determined mainly by the characteristics of brain capillary endothelial membranes. Lipophilic drugs that modify the cell membrane might be anticipated to alter the BBB. We investigated the effect of acute ethanol in combination with either a barbiturate or a non-barbiturate anesthetic on the ability of the rat BBB to exclude circulating horseradish peroxidase (HRP). Rats were injected into the peritoneal cavity with ethanol plus either a barbiturate (pentobarbital) or a non-barbiturate (ketamine hydrochloride) anesthetic. HRP was subsequently injected transcardially 30 s prior to decapitation. In the ethanol plus barbiturate-treated rats focal leakage of HRP caused peroxidase levels in the cerebral cortex to be about 8-fold higher than in ethanol plus ketamine hydrochloride-treated rats. Ultrastructurally endothelial cells in leaking vascular segments were infiltrated with HRP and, in some cases, they were lysed so that the structural integrity of the blood-brain interface was lost. Lysed segments were accompanied by staining of the adjacent basal lamina with HRP, and edematous astrocytic endfeet. These results show that ethanol plus a barbiturate anesthetic causes breakdown in the BBB by structurally damaging brain capillary endothelial cells. Whether the damage is caused by the expansion and lysing of the cell membrane by these two lipophilic drugs, or by increased intracellular calcium to toxic levels is not yet known.
血脑屏障（BBB）的结构和功能主要由脑毛细血管内皮细胞膜的特性决定。能够改变细胞膜的亲脂性药物可能会改变血脑屏障。我们研究了急性乙醇与巴比妥类或非巴比妥类麻醉剂联合使用对大鼠血脑屏障排除循环中的辣根过氧化物酶（HRP）能力的影响。给大鼠腹腔注射乙醇加巴比妥类（戊巴比妥）或非巴比妥类（盐酸氯胺酮）麻醉剂。随后在断头前30秒经心内注射HRP。在乙醇加巴比妥类处理的大鼠中，HRP的局灶性渗漏导致大脑皮质中的过氧化物酶水平比乙醇加盐酸氯胺酮处理的大鼠高约8倍。超微结构显示，渗漏血管段的内皮细胞被HRP浸润，在某些情况下，它们会溶解，从而使血脑界面的结构完整性丧失。溶解的血管段伴有相邻基膜被HRP染色以及星形胶质细胞终足水肿。这些结果表明，乙醇加巴比妥类麻醉剂通过对脑毛细血管内皮细胞造成结构损伤而导致血脑屏障破坏。这种损伤是由这两种亲脂性药物使细胞膜扩张和溶解引起的，还是由细胞内钙升高到毒性水平引起的，目前尚不清楚。
