Butterworth R F
Neuroscience Research Unit, Hôpital Saint-Luc du CHUM, University of Montreal, Montreal, Quebec, Canada.
Indian J Gastroenterol. 2003 Dec;22 Suppl 2:S59-61.
Brain edema and consequent increase in intracranial pressure is a major complication of acute liver failure (ALF) and is a major cause of death in this condition. Rapid accumulation of ammonia in brain has been implicated in the pathogenesis of brain edema in ALF. Increased brain ammonia may cause brain swelling via the osmotic effects of an increase in astrocytic glutamine concentration or by inhibition of glutamate removal from brain extracellular space. Acute liver failure results in altered expression of several genes in the brain, some of which code for proteins involved in central nervous system function such as the glutamate transporter GLT-1, the astrocytic structural protein, glial fibrillary acidic protein, and the water channel protein, aquaporin IV. Loss of expression of GLT-1 results in increased extracellular brain glutamate. Therapeutic measures currently used to prevent and treat brain edema in acute liver failure include mannitol; strategies aimed at lowering of gut ammonia production are generally ineffective. Studies in experimental animals suggest that mild hypothermia or the use of L-ornithine-L-aspartate may be useful in the prevention of brain edema in these patients.
脑水肿以及随之而来的颅内压升高是急性肝衰竭（ALF）的主要并发症，也是导致该病症患者死亡的主要原因。脑内氨的快速蓄积被认为与急性肝衰竭脑水肿的发病机制有关。脑内氨增加可能通过星形胶质细胞谷氨酰胺浓度升高的渗透作用或抑制脑外间隙谷氨酸的清除而导致脑肿胀。急性肝衰竭导致脑内多个基因的表达发生改变，其中一些基因编码参与中枢神经系统功能的蛋白质，如谷氨酸转运体GLT-1、星形胶质细胞结构蛋白胶质纤维酸性蛋白和水通道蛋白水通道蛋白4。GLT-1表达缺失导致脑内细胞外谷氨酸增加。目前用于预防和治疗急性肝衰竭脑水肿的治疗措施包括甘露醇；旨在降低肠道氨生成的策略通常无效。对实验动物的研究表明，轻度低温或使用L-鸟氨酸-L-天冬氨酸可能有助于预防这些患者的脑水肿。
