Cerebral blood flow and the development of ammonia-induced brain edema in rats after portacaval anastomosis

Abstract

Two mechanisms may account for brain edema in fulminant hepatic failure: the osmotic effects of brain glutamine, a product of ammonia detoxification, and a change of cerebral blood flow (CBF). We have shown brain edema, a marked increase in brain glutamine, and a selective rise in CBF in rats after portacaval anastomosis receiving an ammonia infusion. In this study, we inhibited the activity of glutamine synthetase with methionine-sulfoximine (MSO) and examined ammonia levels, brain water and CBF. Four groups received either a continuous ammonium acetate or control infusion; half of the animals had been pretreated with MSO or vehicle. The ammonia group exhibited brain edema (79.97 ± 0.04 vs. 81.11 ± 0.13% water), an increase in cerebrospinal fluid (CSF) glutamine (1.29 ± 0.21 vs. 2.84 ± 0.39 mmol/L) and CBF (63 ± 11 vs. 266 ± 45 mL/min/100 g brain). When MSO was added to the ammonia infusion, ammonia levels rose further (928 ± 51 vs. 1,293 ± 145 mmol/L, P