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  • SAGE Publications  (3)
  • Cunningham, Vincent J.  (3)
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  • SAGE Publications  (3)
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  • 1
    Online Resource
    Online Resource
    SAGE Publications ; 1986
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 6, No. 6 ( 1986-12), p. 708-716
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 6, No. 6 ( 1986-12), p. 708-716
    Abstract: Regional rates of blood–brain glucose transfer and phosphorylation have been measured in anaesthetized fasted and conscious fed and fasted rats using a dual-label 2-deoxyglucose technique that exploits differences in the early-time distribution of analogue and native glucose between blood and brain. Regional cerebral blood flow was also measured in comparable groups of rats. Estimates of glucose influx in the anaesthetized group were compared with those calculated from previously published kinetic constants obtained using [ 14 C]d-glucose as tracer. The close agreement of these two sets of results served to validate estimates of influx obtained using the glucose analogue. Comparisons between all three groups showed that regional rates of glucose influx were maintained at levels appropriate to the rate of cerebral glucose phosphorylation. This occurred despite wide variations in plasma glucose concentration. The results indicate that at least two factors are involved in the adaptation of glucose supply to meet metabolic demand. One is related to blood flow, and probably reflects changes in the surface area of the capillary endothelium perfused. The second involves changes in the blood–brain barrier permeability to glucose and could reflect changes in the density of functioning glucose transporters within capillary endothelial cell membranes.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    Language: English
    Publisher: SAGE Publications
    Publication Date: 1986
    detail.hit.zdb_id: 2039456-1
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  • 2
    Online Resource
    Online Resource
    SAGE Publications ; 1988
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 8, No. 2 ( 1988-04), p. 244-253
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 8, No. 2 ( 1988-04), p. 244-253
    Abstract: The initial distribution of tracer amounts of 2-deoxyglucose between plasma and brain tissue, relative to native glucose, and the rate of accumulation of 2-deoxyglucose-6-phosphate were determined in brain regions of rats given kainic acid intravenously. Regional plasma flow was measured in a comparable group of animals. A previously described compartmental model was used to obtain estimates of rates of glucose transport and of glucose phosphorylation. Both rates were significantly increased in entorhinal cortex, hippocampus, amygdala, and septal nucleus. From measured brain tissue and plasma glucose concentrations, glucose fluxes were also calculated in terms of either irreversible or reversible Michaelis-Menten kinetics. In all brain regions of control rats and in six of the ten regions studied in rats given kainic acid, rates of glucose transport calculated in terms of the Michaelis-Menten models were consistent with those estimated by the tracer 2-deoxyglucose procedure. However, in the four regions in which glucose metabolism was stimulated, rates of glucose transport calculated from the behaviour of tracer 2-deoxyglucose were considerably higher than rates calculated from measured concentrations of glucose in plasma and brain tissue using Michaelis-Menten models. The possibility is considered that in those regions that are metabolically stimulated by kainate, there is an increasing asymmetry between the luminal and abluminal membranes of the capillary endothelium in the permeability to glucose and its analogs. An alternative proposal is that in the model used to analyse the tracer 2-deoxyglucose data, the assumption of a rapid mixing of tracer throughout the endogenous pool of tissue glucose prior to phosphorylation becomes invalid. The discrepancies between tracer and native glucose in these particular regions of rats given kainate are consistent with an apparent metabolic compartmentation. The influence of kainate on plasma flow was found to differ regionally, with flow in entorhinal cortex, hippocampus, and amygdala being unchanged. There is some evidence for increased rates of glycolysis relative to oxidative metabolism in these regions.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    Language: English
    Publisher: SAGE Publications
    Publication Date: 1988
    detail.hit.zdb_id: 2039456-1
    Library Location Call Number Volume/Issue/Year Availability
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  • 3
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 11, No. 1 ( 1991-01), p. 1-9
    Abstract: The regional binding of the opiate receptor ligand diprenorphine has been examined in rat brain both in vivo and in vitro. The time course of total label in specific brain regions was followed up to 2 h after intravenous bolus injection of [ 3 H]diprenorphine, with or without a pulse chase of unlabelled diprenorphine at 30 min. In addition, total label was measured 30 min after injection of labelled diprenorphine at nontracer concentrations over a range of specific activities. Total data sets for each region were fitted simultaneously to a compartmental model to give estimates of maximal binding capacity (B max ), the second-order apparent association rate constant, and the first-order dissociation rate constant of the receptor-ligand complex. The model incorporated the use of a reference region with low specific binding (cerebellum). The binding of diprenorphine to rat brain homogenates was measured in vitro under equilibrium conditions at 37°C, pH 7.4, in the presence and absence of naloxone, to give corresponding regional estimates of B max and the half-saturation constant K d The results showed a close correlation between in vitro and in vivo regional estimates of B max over a wide range. There were no significant interregional differences either in K d in vitro or in the K d derived from the in vivo analysis, although in vitro and in vivo estimates differed by an order of magnitude. This work was carried out as part of a validation study with a view to the application of the compartmental model to data obtained in vivo in humans using positron emission tomography, when successive studies over a range of specific activities are not feasible. Restriction of the rat data to tracer alone and pulse chase protocols showed that the compartmental model gave regional estimates of the combined forward rate constant consistent with estimates obtained using the complete data set.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    Language: English
    Publisher: SAGE Publications
    Publication Date: 1991
    detail.hit.zdb_id: 2039456-1
    Library Location Call Number Volume/Issue/Year Availability
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