Increased brain uptake of gamma-aminobutyric acid in a rabbit model of hepatic encephalopathy

Journal Article · Thu Mar 01 04:00:00 EST 1990 · Gastroenterology; (USA)

OSTI ID:7190589

Bassett, M L; Mullen, K D; Scholz, B; Fenstermacher, J D; Jones, E A ^[1]

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1. National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD (USA)

Transfer of the inhibitory neurotransmitter gamma-aminobutyric acid across the normal blood-brain barrier is minimal. One prerequisite for gamma-aminobutyric acid in plasma contributing to the neural inhibition of hepatic encephalopathy would be that increased transfer of gamma-aminobutyric acid across the blood-brain barrier occurs in liver failure. The aim of the present study was to determine if brain gamma-aminobutyric acid uptake is increased in rabbits with stage II-III (precoma) hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure. A modification of the Oldendorf intracarotid artery-injection technique was applied. (3H) gamma-aminobutyric acid, (14C) butanol, and 113mIn-labeled serum protein (transferrin) were injected simultaneously 4 s before decapitation. The ipsilateral brain uptake index of gamma-aminobutyric acid was determined from measurements of the 3 isotopes in 5 brain regions. Uncorrected or simple brain uptake indices of (3H) gamma-aminobutyric acid and (113mIn) transferrin were calculated using (14C) butanol as the highly extracted reference compound. The (113mIn) transferrin data were also used to correct the brain uptake index of (3H) gamma-aminobutyric acid for intravascular retention of (3H) gamma-aminobutyric acid. The methodology adopted minimized problems attributable to rapid (3H) gamma-aminobutyric acid metabolism, and slow brain washout and recirculation of the radiolabeled tracers. Both the uncorrected and corrected brain uptake indices of gamma-aminobutyric acid as well as the simple brain uptake index of transferrin were significantly increased in both stage II and III hepatic encephalopathy in all brain regions studied. Moreover, these brain uptake indices were significantly greater in stage III hepatic encephalopathy than in stage II hepatic encephalopathy.

• OSTI ID: 7190589
• Journal Information: Gastroenterology; (USA), Journal Name: Gastroenterology; (USA) Vol. 98:3; ISSN GASTA; ISSN 0016-5085
• Country of Publication: United States
• Language: English

Related Subjects

550901* -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALCOHOLS
AMINO ACIDS
AMINOBUTYRIC ACID
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BLOOD-BRAIN BARRIER
BODY
BRAIN
BUTANOLS
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
DIGESTIVE SYSTEM DISEASES
DISEASES
DRUGS
GLOBULINS
GLOBULINS-BETA
HOURS LIVING RADIOISOTOPES
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
INDIUM 113
INDIUM ISOTOPES
INTERMEDIATE MASS NUCLEI
ISOMERIC NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
MAMMALS
MEMBRANE TRANSPORT
METALLOPROTEINS
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PROTEINS
RABBITS
RADIOISOTOPES
STABLE ISOTOPES
TRACER TECHNIQUES
TRANSFERRIN
TRITIUM COMPOUNDS
VERTEBRATES