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Blood-brain barrier permeability in galactosamine-induced hepatic encephalopathy

No evidence for increased GABA-transport
  • Gitte Moos Knudsen
    Correspondence
    Correspondence: Gitte Moos Knudsen, M.D., Department of Neurology N2082, Rigshospitalet, 9 Blegdamsvej, DK-2100 Copenhagen Ø, Denmark. Tel: (45) 1386633, ext. 3279 or 2080.
    Affiliations
    Department of Neurology, Rigshospitalet, Copenhagen (Denmark)
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  • Author Footnotes
    * Present address: Institute of Pharmacology, Copenhagen, Denmark. The work was supported by the Foundation of 17-12-81.
    Henrik Enghusen Poulsen
    Footnotes
    * Present address: Institute of Pharmacology, Copenhagen, Denmark. The work was supported by the Foundation of 17-12-81.
    Affiliations
    Division of Hepatology A, Righospitalet, Copenhagen (Denmark)
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  • Olaf B. Paulson
    Affiliations
    Department of Neurology, Rigshospitalet, Copenhagen (Denmark)
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  • Author Footnotes
    * Present address: Institute of Pharmacology, Copenhagen, Denmark. The work was supported by the Foundation of 17-12-81.
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      Summary

      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 ± 0.02·10−5cm3·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.
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