Ammonia and related amino acids in the pathogenesis of brain edema in acute ischemic liver failure in rats.
The pathogenesis of brain edema in acute liver failure is poorly understood. We have previously shown that rats with ischemic acute liver failure (portacaval anastomosis followed by hepatic artery ligation) exhibit brain edema and intracranial hypertension, with swelling of cortical astrocytes as the most prominent neuropathological abnormality. Because ammonia has been shown to induce swelling of astrocytes in vivo and in vitro, we examined the relationship between brain ammonia, amino acids generated from ammonia metabolism and brain water content in this model. Four groups of animals were studied: rats subjected to two sham operations, rats subjected to portacaval anastomosis and a sham operation, rats subjected to a sham operation and hepatic artery ligation and rats subjected to portacaval anastomosis and hepatic artery ligation. The last group of animals was studied at three progressive stages of encephalopathy. Cortical gray matter water increased from 80.26% +/- 0.22% (sham + sham) to 82.46% +/- 0.06% (last stage of devascularization). In cerebral cortex, brain ammonia increased to a maximum of 5.4 mmol/L. Glutamine, generated in glial cells from ammonia and glutamate, increased sixfold to 24 mmol/L and remained at this level throughout all stages of encephalopathy. Alanine, which may be generated from the transamination of glutamine, increased in parallel to the increase in water (r = 0.80, n = 15). In this model of fulminant liver failure and associated brain edema, brain ammonia increases to levels associated with in vitro swelling of brain slices and glial cells. The accumulation of osmogenic aminoacids such as glutamine and alanine may contribute to the selective astrocyte swelling seen in this condition.(ABSTRACT TRUNCATED AT 250 WORDS)
Swain
M
M
Laboratory of Neurochemistry, Hôpital Saint-Luc, University of Montreal, Quebec.
Butterworth
R F
RF
Blei
A T
AT
D000596:Amino Acids / Q000378:metabolism / Q000502:physiology*; D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology*; D007511:Ischemia / Q000150:complications* / Q000378:metabolism; D008099:Liver / Q000098:blood supply*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000596:Amino Acids; D000641:Ammonia