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Determination of Oxidative Glucose Metabolism In Vivo in the Young Rat Brain Using Localized Direct-Detected 13C NMR Spectroscopy

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Abstract

Determination of oxidative metabolism in the brain using in vivo 13C NMR spectroscopy (13C MRS) typically requires repeated blood sampling throughout the study to measure blood glucose concentration and fractional enrichment (input function). However, drawing blood from small animals, such as young rats, placed deep inside the magnet is technically difficult due to their small total blood volume. In the present study, a custom-built animal holder enabled temporary removal of the animal from the magnet for blood collection, followed by accurate repositioning in the exact presampling position without degradation of B0 shimming. 13C label incorporation into glutamate C4 and C3 positions during a 120 min [1,6-13C2] glucose infusion was determined in 28-day-old rats (n = 4) under α-chloralose sedation using localized, direct-detected in vivo 13C MRS at 9.4T. The tricarboxylic acid cycle activity rate (V TCA) determined using a one-compartment metabolic modeling was 0.67 ± 0.13 μmol/g/min, a value comparable to previous ex vivo studies. This methodology opens the avenue for in vivo measurements of brain metabolic rates using 13C MRS in small animals.

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Acknowledgments

The assistance of Dee Koski and Christopher Nelson with animal preparation, and Anjuli Mishra with GCMS analysis is gratefully acknowledged. Supported in part by grants from the National Institutes of Health (K08 HD47276, R01 NS38672, P41 RR008079, P30 NS057091), University Pediatrics Foundation, Viking Children’s Fund and the Graduate School, University of Minnesota. The 9.4T magnet is funded in part by the W. M. Keck Foundation.

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The authors declare that they have no conflict of interest.

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Correspondence to Raghavendra Rao.

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Ennis, K., Deelchand, D.K., Tkac, I. et al. Determination of Oxidative Glucose Metabolism In Vivo in the Young Rat Brain Using Localized Direct-Detected 13C NMR Spectroscopy. Neurochem Res 36, 1962–1968 (2011). https://doi.org/10.1007/s11064-011-0519-x

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