Zhu XH, Zhang Y, Tian RX, Lei H, Zhang N, Zhang X, Merkle H, Ugurbil K, Chen WDevelopment of (17)O NMR approach for fast imaging of cerebral metabolic rate of oxygen in rat brain at high field. Proc Natl Acad Sci USA 99:13194-13199

University of Minnesota Duluth, Duluth, Minnesota, United States
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 10/2002; 991(20):13194-13199. DOI: 10.1073/pnas.202471399
Source: PubMed


A comprehensive technique was developed for using three-dimensional 17O magnetic resonance spectroscopic imaging at 9.4T for rapidly imaging the cerebral metabolic rate of oxygen consumption (CMRO2) in the rat brain during a two-min inhalation of 17O2. The CMRO2 value (2.19 ± 0.14 mumol/g/min, n = 7) was determined in the rat anesthetized with -chloralose by independent and concurrent 17O NMR measurements of cerebral H217O content, arterial input function, and cerebral perfusion. CMRO2 values obtained were consistent with the literature results for similar conditions. Our results reveal that, because of its superior sensitivity at ultra-high fields, the 17O magnetic resonance spectroscopic imaging approach is capable of detecting small dynamic changes of metabolic H217O during a short inhalation of 17O2 gas, and ultimately, for imaging CMRO2 in the small rat brain. This study provides a crucial step toward the goal of developing a robust and noninvasive 17O NMR approach for imaging CMRO2 in animal and human brains that can be used for studying the central role of oxidative metabolism in brain function under normal and diseased conditions, as well as for understanding the mechanisms underlying functional MRI.

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    • "Baseline values of tpO 2 and CBF were taken as the mean of a 20 s period obtained before the onset of stimulation. These values were then combined with reported values for CBF and CMRO 2 previously obtained (Zhu et al., 2002) in rats (53 ml ( "
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    ABSTRACT: Evoked neural activity correlates strongly with rises in cerebral metabolic rate of oxygen (CMRO(2)) and cerebral blood flow (CBF). Activity-dependent rises in CMRO(2) fluctuate with ATP turnover due to ion pumping. In vitro studies suggest that increases in cytosolic Ca(2+) stimulate oxidative metabolism via mitochondrial signaling, but whether this also occurs in the intact brain is unknown. Here we applied a pharmacological approach to dissect the effects of ionic currents and cytosolic Ca(2+) rises of neuronal origin on activity-dependent rises in CMRO(2). We used two-photon microscopy and current source density analysis to study real-time Ca(2+) dynamics and transmembrane ionic currents in relation to CMRO(2) in the mouse cerebellar cortex in vivo. We report a direct correlation between CMRO(2) and summed (i.e., the sum of excitatory, negative currents during the whole stimulation period) field EPSCs (∑fEPSCs) in Purkinje cells (PCs) in response to stimulation of the climbing fiber (CF) pathway. Blocking stimulus-evoked rises in cytosolic Ca(2+) in PCs with the P/Q-type channel blocker ω-agatoxin-IVA (ω-AGA), or the GABA(A) receptor agonist muscimol, did not lead to a time-locked reduction in CMRO(2), and excitatory synaptic or action potential currents. During stimulation, neither ω-AGA or (μ-oxo)-bis-(trans-formatotetramine-ruthenium) (Ru360), a mitochondrial Ca(2+) uniporter inhibitor, affected the ratio of CMRO(2) to fEPSCs or evoked local field potentials. However, baseline CBF and CMRO(2) decreased gradually with Ru360. Our data suggest that in vivo activity-dependent rises in CMRO(2) are correlated with synaptic currents and postsynaptic spiking in PCs. Our study did not reveal a unique role of neuronal cytosolic Ca(2+) signals in controlling CMRO(2) increases during CF stimulation.
    Full-text · Article · Dec 2011 · The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
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    • "Where tP O 2 is the tissue oxygen tension, P 50 is the half-saturation tension of the oxygen– hemoglobin dissociation curve, h is the Hill coefficient of the same dissociation curve, C a is the arterial oxygen concentration, and L is the effective diffusion coefficient of oxygen in brain tissue. The value of L was determined from baseline values of rats in similar conditions of anesthesia in which CBF and CMRO 2 were reported in the literature to be 53 ml·100 g −1 ·min −1 and 219 μmol·100 g −1 ·min −1 (Zhu et al., 2002). The corresponding value of L was 5.45 μmol·100g −1 ·min −1 ·mmHg −1 for standard values of P 50 (36 mmHg), h (2.7), and C a (8 μmol ml −1 ). "
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    ABSTRACT: Epileptic events initiate a large focal increase in metabolism and cerebral blood flow (CBF) to the ictal focus. In contrast, decreases in CBF have been demonstrated surrounding the focus, the etiology of which is unknown (i.e., arising either from active shunting of blood or passive steal). The relationship between these events and neuronal activity and metabolism are also unknown. We investigated neurovascular and neurometabolic coupling in the ictal surround using optical imaging of light scattering and cerebral blood volume, autofluorescence flavoprotein imaging (AFI), direct measurements of the cortical metabolic rate of oxygen and two-photon imaging of blood vessel diameter in a rat model of ictal events elicited with focal injection of 4-aminopyridine. We discovered a novel phenomenon, in which ictal events are preceded by preictal vasoconstriction of blood vessels in the surround, occurring 1-5 s before seizure onset, which may serve to actively shunt oxygenated blood to the imminently hypermetabolic focus or may be due to small local decreases in metabolism in the surround. Early ictal hypometabolism, transient decreases in cell swelling and cerebral blood volume in the surround are consistent with early ictal surround inhibition as a precipitating event in seizure onset as well as shaping the evolving propagating ictal wavefront, although the exact mechanism of these cerebrovascular and metabolic changes is currently unknown. AFI was extremely sensitive to the ictal onset zone and may be a useful mapping technique with clinical applications.
    Full-text · Article · Sep 2011 · The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
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    • "), in agreement to other determinations by 13 C NMR (Henry et al., 2002), or to measurements of CMR O2 by 17 O NMR spectroscopy (Zhu et al., 2002) and CMR glc by autoradiography (Ueki et al., 1992; Nakao et al., 2001) in rats under α-chloralose anesthesia. The neurotransmission flux V NT represents the flow of 13 C labeling in the glutamate–glutamine cycle and was now determined to be 0.11 ± 0.01 μmol/g/min (see Table 1) that is similar to that reported by (Sibson et al., 1998) for the rat brain under α-chloralose anesthesia. "
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    ABSTRACT: Cerebral metabolism is compartmentalized between neurons and glia. Although glial glycolysis is thought to largely sustain the energetic requirements of neurotransmission while oxidative metabolism takes place mainly in neurons, this hypothesis is matter of debate. The compartmentalization of cerebral metabolic fluxes can be determined by (13)C nuclear magnetic resonance (NMR) spectroscopy upon infusion of (13)C-enriched compounds, especially glucose. Rats under light α-chloralose anesthesia were infused with [1,6-(13)C]glucose and (13)C enrichment in the brain metabolites was measured by (13)C NMR spectroscopy with high sensitivity and spectral resolution at 14.1 T. This allowed determining (13)C enrichment curves of amino acid carbons with high reproducibility and to reliably estimate cerebral metabolic fluxes (mean error of 8%). We further found that TCA cycle intermediates are not required for flux determination in mathematical models of brain metabolism. Neuronal tricarboxylic acid cycle rate (V(TCA)) and neurotransmission rate (V(NT)) were 0.45 ± 0.01 and 0.11 ± 0.01 μmol/g/min, respectively. Glial V(TCA) was found to be 38 ± 3% of total cerebral oxidative metabolism, accounting for more than half of neuronal oxidative metabolism. Furthermore, glial anaplerotic pyruvate carboxylation rate (V(PC)) was 0.069 ± 0.004 μmol/g/min, i.e., 25 ± 1% of the glial TCA cycle rate. These results support a role of glial cells as active partners of neurons during synaptic transmission beyond glycolytic metabolism.
    Full-text · Article · Jun 2011 · Frontiers in Neuroenergetics
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