title: Blood-brain barrier permeability in galactosamine-induced hepatic encephalopathy. No evidence for increased GABA-transport.
abstract: Blood-brain barrier permeability to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), to sucrose and to sodium was studied in rats with galactosamine-induced liver damage and hepatic encephalopathy by means of an arterial integral uptake technique. Permeability to GABA was unaltered in all examined brain regions (2.47 +/- 0.25.10(-5) cm3.s-1.g-1, mean +/- S.D.) as compared to control rats (2.49 +/- 0.19.10(-5) cm3.s-1.g-1). The permeability to sucrose (galactosamine 0.25 +/- 0.02 vs. controls 0.24 +/- 0.02.10(-5) cm3.s-1.g-1) and to sodium (galactosamine 5.33 +/- 0.04 vs. controls 5.40 +/- 0.05.10(-5) cm3.s-1.g-1) was also unchanged in hepatic encephalopathy. At the time of investigation mean liver function measured by antipyrine clearance was reduced from 0.39 in control rats to 0.23 ml/min/100 g body wt. in galactosamine-treated animals. The present study does not support the suggestion that peripheral GABA penetrates the blood-brain barrier to any higher extent in hepatic encephalopathy. This provides evidence against at least part of the GABA-hypothesis. Furthermore, an unspecific increased blood-brain barrier permeability in hepatic encephalopathy, as measured by sucrose and sodium uptake, was not found. It is concluded that the GABA-theory requires further careful reevaluation.
authors.affiliation: Department of Neurology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: G M
authors.initials: GM
authors.lastname: Knudsen
authors.forename: H E
authors.initials: HE
authors.lastname: Poulsen
authors.forename: O B
authors.initials: OB
authors.lastname: Paulson
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D005688:Galactosamine; D006501:Hepatic Encephalopathy / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000493:pharmacokinetics; D013395:Sucrose / Q000493:pharmacokinetics; D005680:gamma-Aminobutyric Acid / Q000493:pharmacokinetics*
chemical_list: D005680:gamma-Aminobutyric Acid; D013395:Sucrose; D005688:Galactosamine; D012964:Sodium