Alterations in neutral amino acid transport across the blood-brain barrier in hepatic failure.
The accelerated transport of the blood neutral amino acids into the brain in encephalopathic patients with fulminant hepatitis and advanced liver cirrhosis was demonstrated not only by determining the cerebrospinal fluid (CSF) aminogram but also by calculating the predicted velocity of the amino acid transport through the blood-brain barrier. Significant elevation in CSF aromatic amino acid (AAA) and methionine levels was observed in the encephalopathic patients. Arousal from hepatic encephalopathy by drip infusion of a branched chain amino acid (BCAA)-enriched solution was obtained coincidentally with the elevated BCAA levels and diminished concentrations of AAA and methionine in CSF. These clinical observations were confirmed experimentally in rats treated with carbon tetrachloride (CCl4) and D-galactosamine by obtaining the elevation of neutral amino acid contents in the brain and the slight increase in the brain uptake index (BUI) of a radiolabeled amino acid.