title: Suppression of ammonia-induced swelling by aspartate but not by ornithine in primary cultures of rat astrocytes.
abstract: Cerebral edema with a rise in intracranial pressure is the hallmark of fulminant hepatic failure (FHF) and acute hyperammonemic (HA) states and is characterized by a poor survival rate. Astrocytes are the cells in brain which are swollen in these conditions. Several hypotheses have been proposed to explain the mechanism of cerebral edema in FHF and treatment strategies have evolved based on these putative mechanisms. Treatment with a mixture of ornithine and aspartate has been proven to be clinically beneficial as it reduces edema and improves the neurological status. It has been suggested that these two amino acids generate the glutamate required for the synthesis of glutamine and that they also enhance urea synthesis in surviving hepatocytes in FHF and HA. Presently, we report that of these two amino acids, only aspartate is effective in suppressing ammonia-induced swelling in primary cultures of astrocytes, while ornithine is ineffective. These results are discussed in relation to the metabolism of aspartate and ornithine in astrocytes, with an emphasis on glutamine synthesis and the malate-aspartate shuttle (MAS). We propose that the ability of aspartate to generate glutamate in the cytosol for glutamine synthesis and oxaloacetate in mitochondria to support the citric acid cycle play a role in its ability to reduce ammonia-induced swelling in astrocytes.
authors.affiliation: Department of Animal Sciences, University of Hyderabad, Andhra Pradesh, Hyderabad, India.
authors.forename: Chinta R K
authors.initials: CR
authors.lastname: Murthy
authors.forename: Michael D
authors.initials: MD
authors.lastname: Norenberg
mesh_terms: D000643:Ammonium Chloride / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology*; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects*; D002478:Cells, Cultured; D018920:Coculture Techniques; D009952:Ornithine / Q000494:pharmacology*; D051381:Rats
chemical_list: D000643:Ammonium Chloride; D001224:Aspartic Acid; D009952:Ornithine