Biomedical subjects

Robin A de Graaf

Publications and source records attributed to Robin A de Graaf.

21 records · Page 2Linked to original sources

PubMed2002

[2,4-13 C2 ]-beta-Hydroxybutyrate metabolism in human brain.

Infusions of [2,4-13C2]-beta-hydroxybutyrate and 1H-13C polarization transfer spectroscopy were used in normal human subjects to detect the entry and metabolism of beta-hydroxybutyrate in the brain. During the 2-hour infusion study, 13C label was detectable in the beta-hydroxybutyrate resonance positions and in the amino acid pools of glutamate, glutamine, and aspartate. With a plasma concentration of 2.25 +/- 0.24 mmol/L (four volunteers), the apparent tissue beta-hydroxybutyrate concentration reached 0.18 +/- 0.06 mmol/L during the last 20 minutes of the study. The relative fractional enrichment of 13C-4-glutamate labeling was 6.78 +/- 1.71%, whereas 13C-4-glutamine was 5.68 +/- 1.84%. Steady-state modeling of the 13C label distribution in glutamate and glutamine suggests that, under these conditions, the consumption of the beta-hydroxybutyrate is predominantly neuronal, used at a rate of 0.032 +/- 0.009 mmol. kg-1. min-1, and accounts for 6.4 +/- 1.6% of total acetyl coenzyme A oxidation. These results are consistent with minimal accumulation of cerebral ketones with rapid utilization, implying blood-brain barrier control of ketone oxidation in the nonfasted adult human brain.

3-Hydroxybutyric Acid↗

PubMedDate not supplied

Cerebral pyruvate carboxylase flux is unaltered during bicuculline-seizures.

Glutamine synthesis in the astroglia reflects the sum of neurotransmitter cycling (glutamate and gamma-aminobutyric acid [GABA]) and de novo synthesis (anaplerosis), the latter catalyzed by pyruvate carboxylase. Previous studies have shown that the glutamate plus GABA cycling flux is correlated strongly with neuronal activity; however, the relationship between pyruvate carboxylase flux and neuronal activity is not known. In this study, pyruvate carboxylase flux was assessed during intravenous infusion of [2-(13)C]glucose using localized (1)H-[(13)C] NMR spectroscopy at 7 Tesla in vivo in halothane-anesthetized and ventilated adult Wistar rats during 85 min of bicuculline-induced seizures (1 mg/kg, intravenously) and in nontreated controls. During seizures, concentrations of lactate, alanine, glutamine, GABA, and succinate increased whereas glutamate and aspartate decreased such that the decrease in glutamate plus aspartate equaled the increase in glutamine plus GABA. Pyruvate carboxylase flux was assessed by the sum of [2-(13)C] and [3-(13)C] of glutamine and glutamate (Glx(2+3)) labeling during [2-(13)C]glucose infusion. During seizures the initial rate of Glx(2+3) synthesis (0.069 +/- 0.013 micromol/g/min) was not significantly different (P = 0.68) from that of the controls (0.059 +/- 0.010 micromol/g/min), indicating that anaplerotic flow through pyruvate carboxylase was unaltered. Intense neuronal activation of seizures did not seem to increase anaplerosis through pyruvate carboxylase, despite the substantial increase in neuronal activity and glutamate/glutamine cycling shown in a previous study (Patel et al., 2004b).

Amino Acids↗

PubMedDate not supplied

In vivo 1H-[13C]-NMR spectroscopy of cerebral metabolism.

13C NMR spectroscopy in combination with the infusion of (13)C-labeled precursors is currently the only technique that is capable of quantitatively studying energy metabolism, neurotransmission and other metabolic pathways non-invasively in vivo. (1)H-[(13)C]-NMR spectroscopy is a high-sensitivity alternative to direct (13)C NMR spectroscopy. The development of improved NMR methods for water suppression, spatial localization, broadband decoupling, shimming and signal quantification, together with the availability of high magnetic field strengths, has made (1)H-[(13)C]-NMR spectroscopy the method of choice for the detection of metabolism at a high spatial and/or temporal resolution. (1)H-[(13)C]-NMR spectroscopy can now be used to discriminate glutamatergic (excitatory) and GABAergic (inhibitory) neuronal activity. The improved sensitivity allows the detection of metabolism in different tissues (e.g. gray and white matter) and potentially even in smaller structures, like cortical layers. Finally, (1)H-[(13)C]-NMR spectroscopy allows the detection of energy metabolism and neurotransmission during functional activation, thereby further strengthening our understanding of the neurochemical basis of brain function.

Algorithms↗