Evaluating early changes in cerebral metabolism in hydrocephalus can help in the decision making and the timing of surgical intervention. This study was aimed at examining the tricarboxylic acid (TCA) cycle rate and 13C label incorporation into neurotransmitter amino acids and other compounds 2 weeks after rats were subjected to kaolin-induced progressive hydrocephalus. In vivo and ex vivo magnetic resonance spectroscopy (MRS), combined with the infusion of [1,6- 13C]glucose, was used to monitor the time courses of 13C label incorporation into the different carbon positions of glutamate in the forebrains of rats with hydrocephalus as well as in those of controls. Metabolic rates were determined by fitting the measured data into a one-compartment metabolic model. The TCA cycle rate was 1.3 ± 0.2 lmoles/gram/minute in the controls and 0.8 ± 0.4 lmoles/gram/minute in the acute hydrocephalus group, the exchange rate between a-ketoglutarate and glutamate was 4.1 ± 2.5 lmoles/gram/minute in the controls and 2.7 ± 2.6 lmoles/gram/minute inthe hydrocephalus group calculated from in vivo MRS. There were no statistically significant differences between these rates. Hydrocephalus caused a decrease in the amounts of glutamate, alanine and taurine. In addition, the concentration of the neuronal marker N-acetyl aspartate was decreased. 13C Labelling of most amino acids derived from [1,6- 13C]glucose was unchanged 2 weeks after hydrocephalus induction. The only indication of astrocyte impairment was the decreased 13C enrichment in glutamine C-2. This study shows that hydrocephalus causes subtle but significant alterations in neuronal metabolism already early in the course of the disease. These sub-lethal changes, however, if maintained and if ongoing might explain the delayed and programmed neuronal damage as seen in chronic hydrocephalus.
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Acknowledgments The authors would like to thank Tore W. Mei-singseth, Sivert H. Sandvik and Tina B. Pedersen for practical help with the bench experiment. Pierre-Gilles Henry wishes to acknowledge support from NIH grant R01 NS38672.
- In vivo C MR spectroscopy