13C Nuclear Magnetic Resonance spectroscopy is the method of choice for studying brain metabolism. Indeed, the most convincing data obtained to decipher metabolic exchanges between neurons and astrocytes have been obtained using this technique, thus illustrating its power. It may be difficult for non-specialists, however, to grasp the full implication of data presented in articles written by spectroscopists. The aim of the review is, therefore, to provide a fundamental understanding of this topic to facilitate the non-specialists in their reading of this literature. In the first part of this review, we present the metabolic fate of 13 C-labelled substrates in the brain in a detailed way, including an overview of some general neurochemical principles. We also address and compare the various spectroscopic strategies that can be used to study brain metabolism. Then, we provide an overview of the 13 C Nuclear Magnetic Resonance experiments performed to analyse both intracellular and intercellular metabolic fluxes. More particularly, the role of lactate as a potential energy substrate for neurons is discussed in the light of 13 C Nuclear Magnetic Resonance data. Finally, new perspectives and applications offered by 13 C hyperpolarization are described.

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13C NMR spectroscopy applications to brain energy metabolism

Phosphorylethanolamine (PEA) is the major component of the phosphomonoester peak detected by phosphorus-31 magnetic resonance spectroscopy, but the absolute concentration has not been determined. This study measured the PEA concentration in biopsy specimens of brain tumors and lobectomized cerebral cortex using high-performance liquid chromatography. The concentration of PEA was 118.5 ± 10.0 μmol/100 g wet wt in cortex, and was significantly higher in malignant gliomas, metastatic pulmonary adenocarcinoma, and neurinoma. The concentration of PEA was especially high in pituitary adenoma, malignant lymphoma, and medulloblastoma.

Phosphorylethanolamine content of human brain tumors.

This work was supported in part by grants SAF 2001‐224, SAF 2004‐03197, FISss C03/08, G03/155, C03/10 and PI051530 to S.C. JUSTESA IMAGEN S.A. provided the core support of LISMAR during this work. T.B. R was supported by a fellowship from Fundacâo para a Ciencia e Tecnologia, Portugal (SFRH/BD/5407/2001).

The cerebral tricarboxylic acid cycles

One of the greatest merits of nuclear magnetic resonance (NMR) methodology used in biomedical research and clinical settings is its capability of measuring various physiological parameters in vivo. Besides MR imaging (MRI), which has been routinely applied to obtain vital information in living organs at normal and diseased states, in vivo MR spectroscopy (MRS) provides an invaluable tool for determining metabolites, chemical reaction rates, bioenergetics, and their dynamic changes in the human and animals noninvasively. These MRS capabilities are further enhanced at high/ultrahigh magnetic fields because of significant gain in NMR detection sensitivity and improvement in the spectral resolution. Recent progress has shown that in vivo MRS holds great promise in many biomedical research areas—in particular, brain research. This article provides a broad review of (i) in vivo multinuclear MRS approaches, (ii) advanced MRS methodologies, and (iii) MRS applications for determining cerebral metabolism as well as bioenergetics at resting brain state and their dynamic changes in response to brain activation. © 2005 Wiley Periodicals, Inc. Concepts Magn Reson Part A 27A: 84-121, 2005

Dynamic study of cerebral bioenergetics and brain function using in vivo multinuclear MRS approaches

The greatest merit of in vivo magnetic resonance spectroscopy (MRS) methodology used in biomedical research is its ability for noninvasively measuring a variety of metabolites inside a living organ It, therefore, provides an invaluable tool for determining metabolites, chemical reaction rates and bioenergetics, as well as their dynamic changes in the human and animal The capability of in vivo MRS is further enhanced at higher magnetic fields because of significant gain in detection sensitivity and improvement in the spectral resolution Recent progress of in vivo MRS technology has further demonstrated its great potential in many biomedical research areas, particularly in brain research Here, we provide a review of new developments for in vivo heteronuclear 31P and 17O MRS approaches and their applications in determining the cerebral metabolic rates of oxygen and ATP inside the mitochondria, in both animal and human brains

/pdf/advanced-in-vivo-heteronuclear-mrs-approaches-for-studying-5fr9dmggrw.pdf

Advanced In Vivo Heteronuclear MRS Approaches for Studying Brain Bioenergetics Driven by Mitochondria.

Cerebral metabolism and neuronal function of prefrontal brain cortex were studied in 6 dog litters from birth to 3 months of age. Noninvasive phosphorus magnetic resonance spectroscopy (31P-MRS) was used to observe longitudinal biochemical changes in the phosphorus compounds associated with cerebral metabolism. Neurological tests, examining reflex, motor and sensory nerve function, were performed in conjunction with the 31P-MRS study. During the neonatal period, exponential increases in PCr, Pi, and phophodiesters preceded neurological changes. Phosphomonoesters showed an exponential, nearly linear, decrease and PCr/Pi was maintained during the 3-month period. Developmental increases in high energy phosphates and the maintenance of PCr/Pi indicate that the increased energy demands of the developing animal are met by increased mitochondrial function (ATP turnover).

31P magnetic resonance spectroscopy study of cerebral metabolism in developing dog brain and its relationship to neuronal function

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31P magnetic resonance spectroscopy study of cerebral metabolism in developing dog brain and its relationship to neuronal function