It is well established that lactate can be used as an energy substrate by the brain by conversion to pyruvate and a subsequent oxidation in the mitochondria. Knowing the need for readily metabolizable substrates directly after ischemia and the protective effect of lactate after excitotoxicity, the aim of this study was to investigate whether lactate administration directly after ischemia could be neuroprotective. In vitro, the addition of 4 mmol/L l-lactate to the medium of rat organotypic hippocampal slices, directly after oxygen and glucose deprivation (OGD), protected against neuronal death, whereas a higher dose of 20 mmol/L was toxic. In vivo, after middle cerebral artery occlusion in the mouse, an intracerebroventricular injection of 2 μL of 100 mmol/L l-lactate, immediately after reperfusion, led to a significant decrease in lesion size, which was more pronounced in the striatum, and an improvement in neurologic outcome. A later injection 1 h after reperfusion did not reduce lesion size, but significantly improved neurologic outcome, which is an important point in the context of a potential clinical application. Therefore, a moderate increase in lactate after ischemia may be a therapeutic tool.

Localized ¹³C NMR spectroscopy provides a new investigative tool for studying cerebral metabolism. The application of ¹³C NMR spectroscopy to living intact humans and animals presents the investigator with a number of unique challenges. This review provides in the first part a tutorial insight into the ingredients required for achieving a successful implementation of localized ¹³C NMR spectroscopy. The difficulties in establishing ¹³C NMR are the need for decoupling of the one‐bond ¹³C–¹H heteronuclear J coupling, the large chemical shift range, the low sensitivity and the need for localization of the signals. The methodological consequences of these technical problems are discussed, particularly with respect to (a) RF front‐end considerations, (b) localization methods, (c) the low sensitivity, and (d) quantification methods. Lastly, some achievements of in vivo localized ¹³C NMR spectroscopy of the brain are reviewed, such as: (a) the measurement of brain glutamine synthesis and the feasibility of quantifying glutamatergic action in the brain; (b) the demonstration of significant anaplerotic fluxes in the brain; (c) the demonstration of a highly regulated malate‐aspartate shuttle in brain energy metabolism and isotope flux; (d) quantification of neuronal and glial energy metabolism; and (e) brain glycogen metabolism in hypoglycemia in rats and humans. We conclude that the unique and novel insights provided by ¹³C NMR spectroscopy have opened many new research areas that are likely to improve the understanding of brain carbohydrate metabolism in health and disease. Copyright © 2003 John Wiley & Sons, Ltd.

The effect of deep barbiturate anesthesia on brain glucose transport, TCA cycle flux, and aspartate, glutamate, and glutamine metabolism was assessed in the rat brain in vivo using ¹³C nuclear magnetic resonance spectroscopy at 9.4 T in conjunction with [1-¹³C] glucose infusions. Brain glucose concentrations were elevated, consistent with a twofold reduced cerebral metabolic rate for glucose (CMR_glc) compared with light α-chloralose anesthesia. Using a mathematical model of neurotransmitter metabolism, several metabolic reaction rates were extracted from the rate of label incorporation. Total oxidative glucose metabolism, CMR_glc(ox), was 0.33 ± 0.03 μmol·g⁻¹ · min⁻¹. The neuronal TCA cycle rate was similar to that in the glia, 0.35 ± 0.03 μmol · g⁻¹ · min⁻¹ and 0.26 ± 0.06 μmol · g⁻¹ · min⁻¹, respectively, suggesting that neuronal energy metabolism was mainly affected. The rate of pyruvate carboxylation was 0.03 ± 0.01 μmol·g⁻¹ · min⁻¹. The exchange rate between cytosolic glutamate and mitochondrial 2-oxoglutarate, V_x, was equal to the rate of neuronal pyruvate dehydrogenase flux. This indicates that V_x is coupled to CMR_glc(ox), implying that the malate-aspartate shuttle is the major mechanism that facilitates label exchange across the inner mitochondrial membrane. The apparent rate of glutamatergic neurotransmission, V_NT, was 0.04 ± 0.01 μmol·g⁻¹ · min⁻¹, consistent with strong reductions in electrical activity. However, the rates of cerebral oxidative glucose metabolism and glutamatergic neurotransmission, CMR_glc(ox)/V_NT, did not correlate with a 1:1 stoichiometry.