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13C-MRS studies on cerebral metabolism

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13C from labeled glucose is normally incorporated rapidly into cerebral glutamate with little detectable glutamine or citrate. In contrast, glutamine and citrate only show significant labeling from13C acetate, which reflects metabolism in glial cells. When brain slices are depolarized with 40 mM KC1 (which mirrors some of the conditions of epilepsy) the13C enrichment of glutamine and citrate from glucose is accelerated in contrast to that of glutamate, which is not. This clearly indicates that depolarizing conditions stimulate glial rather than neuronal consumption of glucose.

In tissues subjected to hypoxia, there is greatly increased labeling of glycerol 3-phosphate, which was confirmed by its increased presence in31P-MR (magnetic resonance) spectra. Analysis of the labeling of lactate, alanine, and glycerol 3-phosphate demonstrated that the ability of the brain to maintain normal function in hypoxia is limited by the capacity of the key enzyme, lactate dehydrogenase. This has implications in the clinical assessment and management of stroke. These results also have implications in the interpretation of activation studies, where increased lactate could be due either to depolarization or hypoxia, or both.

The spectra observed in studies on metabolism of U-[13C] glutamate in cerebral preparations revealed clear signals from glutamine and lactate released to the media. The isotopomer patterns of the lactate showed that it must have arisen from the exogenous glutamate, because if it were due to naturally abundant13C in the lactate, only singlets would have appeared. Comparison of the isotopomer patterns and the percentage13C enrichments of the glutamine and lactate showed that there is higher incorporation of13C from exogenous glutamate into lactate than into glutamine. The enrichment of the lactate indicated that very little was derived from glucose and suggests that the glutamate is converted to lactate in the glia for use by the neurones.

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Correspondence to Herman Bachelard.

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Bachelard, H., Badar-Goffer, R., Ben-Yoseph, O. et al. 13C-MRS studies on cerebral metabolism. MAGMA 2, 285–289 (1994). https://doi.org/10.1007/BF01705254

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  • Glucose
  • Lactate
  • Citrate
  • Glutamate
  • Glutamine