Increased blood-brain transfer in a rabbit model of acute liver failure

Marc E. Horowitz, Daniel F. Schafer, Peter Molnar, E. Anthony Jones, Ronald G. Blasberg, Clifford S. Patlak, Jeanne Waggoner, Joseph D. Fenstermacher

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109 Scopus citations

Abstract

The blood-to-brain transfer of [14C]α-aminoisobutyric acid was investigated by quantitative autoradiography in normal rabbits and rabbits with acute liver failure induced by the selective hepatotoxin galactosamine. The blood-to-brain transfer of α-aminoisobutyric acid was similar in control animals and animals 2 and 7 h after galactosamine injections, but was increased five- to tenfold in certain gray-matter areas of the brain in animals 11 and 18 h after galactosamine treatment. No detectable differences in white-matter uptake of [14C] α-aminoisobutyric acid were found between the control and treated groups. The increase in α-aminoisobutyric acid transfer within the gray-matter areas suggested that a general or nonspecific increase in brain capillary permeability occurred in these areas. No clinical signs of early hepatic encephalopathy were observed in the treated rabbits, except for 1 animal from the 18-h postgalactosamine group. Thus, enhanced blood-brain transfer of α-aminoisobutyric acid preceded the development of overt hepatic encephalopathy. The distribution of radioactivity after the intravenous administration of [14C]galactosamine showed that virtually none of the hepatotoxin localized in the brain, suggesting that the drug itself does not have a direct effect upon the blood-brain barrier or the brain. The increased uptake of α-aminoisobutyric acid at 11 and 18 h implies that the transfer of other solutes would also be enhanced, that central nervous system homeostasis would be compromised, and that the resulting changes in brain fluid composition could contribute to or cause hepatic encephalopathy.

Original languageEnglish (US)
Pages (from-to)1003-1011
Number of pages9
JournalGastroenterology
Volume84
Issue number5 PART 1
DOIs
StatePublished - May 1983

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Horowitz, M. E., Schafer, D. F., Molnar, P., Jones, E. A., Blasberg, R. G., Patlak, C. S., Waggoner, J., & Fenstermacher, J. D. (1983). Increased blood-brain transfer in a rabbit model of acute liver failure. Gastroenterology, 84(5 PART 1), 1003-1011. https://doi.org/10.1016/0016-5085(83)90203-2