Tominaga S, Watanabe A, Tsuji T
First Department of Internal Medicine, Okayama University Medical School, Japan.
Metab Brain Dis. 1991 Jun;6(2):93-105. doi: 10.1007/BF00999907.
The effects of cytotoxic substances such as ammonia, bile acids and endotoxin, all of which increase in the circulating blood during fulminant hepatic failure (FHF), on the blood-brain barrier (BBB) permeability and development of brain edema were examined in the rats. Direct intracarotid injection of various bile acids resulted in the staining of the cerebral hemisphere with Evans blue as well as the increase of brain water contents. Elevation of ammonia was also observed in the cerebral hemisphere where the reversible opening of the BBB was induced by deoxycholate under hyperammonemic conditions. To see the synergistic significance of cytotoxic substances (ammonia, bile acid and endotoxin) under the more physiological condition as FHF, they were simultaneously injected into a peripheral vein. Brain uptake index of 14C-inulin and brain water content increased, and electron micrographs showed the swollen astrocytic foot processes surrounded brain capillary, but not opening of tight junction, the same as an animal model of fulminant hepatic failure. The results suggest that ammonia, bile acids and endotoxin might have a possible synergistic role in the pathogenesis of the brain edema, mainly cytotoxic, and vasogenic due to acceleration of vesicular transport, in FHF.
在大鼠中研究了细胞毒性物质如氨、胆汁酸和内毒素（在暴发性肝衰竭（FHF）期间循环血液中这些物质均会增加）对血脑屏障（BBB）通透性及脑水肿形成的影响。直接经颈内动脉注射各种胆汁酸会导致大脑半球被伊文思蓝染色，同时脑含水量增加。在高氨血症条件下，脱氧胆酸盐诱导血脑屏障可逆性开放的大脑半球中也观察到氨水平升高。为了在更接近FHF的生理条件下观察细胞毒性物质（氨、胆汁酸和内毒素）的协同作用，将它们同时注入外周静脉。14C-菊粉的脑摄取指数和脑含水量增加，电子显微镜照片显示肿胀的星形胶质细胞足突围绕脑毛细血管，但紧密连接未开放，这与暴发性肝衰竭动物模型相同。结果表明，氨、胆汁酸和内毒素在FHF脑水肿的发病机制中可能具有协同作用，主要是细胞毒性作用，并且由于囊泡运输加速而具有血管源性作用。
