Brain development:1H magnetic resonance spectroscopy of rat brain extracts compared with chromatographic methods

Burri, Roland; Bigler, Peter; Straehl, Peter; Posse, Stefan; Colombo, Jean‐Pierre; Herschkowitz, N

doi:10.1007/bf00965747

Cited by 71 publications

(51 citation statements)

References 28 publications

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“…It is a postulated source of acetate for lipid and myelin synthesis of oligodendrocytes (Satrustegui et al, 2007). As the immature rat brain develops, rapid increases in NAA are detected during the time of peak myelination (D'Adamo and Yatsu, 1966;Bates et al, 1989;Burri et al, 1990). Using purified rat brain mitochondria (Patel and Clark, 1979), the synthesis and transport of NAA out of mitochondria increased with brain development in concert with myelination.…”

Section: Discussionmentioning

confidence: 99%

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Early and Sustained Alterations in Cerebral Metabolism after Traumatic Brain Injury in Immature Rats

Casey

McKenna

Fiskum

et al. 2008

Journal of Neurotrauma

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Although studies have shown alterations in cerebral metabolism after traumatic brain injury (TBI), clinical data in the developing brain is limited. We hypothesized that post-traumatic metabolic changes occur early (Ͻ24 h) and persist for up to 1 week. Immature rats underwent TBI to the left parietal cortex. Brains were removed at 4 h, 24 h, and 7 days after injury, and separated into ipsilateral (injured) and contralateral (control) hemispheres. Proton nuclear magnetic resonance (NMR) spectra were obtained, and spectra were analyzed for N-acetyl-aspartate (NAA), lactate (Lac), creatine (Cr), choline, and alanine, with metabolite ratios determined (NAA/Cr, Lac/Cr). There were no metabolic differences at any time in sham controls between cerebral hemispheres. At 4 and 24 h, there was an increase in Lac/Cr, reflecting increased glycolysis and/or decreased oxidative metabolism. At 24 h and 7 days, there was a decrease in NAA/Cr, indicating loss of neuronal integrity. The NAA/Lac ratio was decreased (ϳ15-20%) at all times (4 h, 24 h, 7 days) in the injured hemisphere of TBI rats. In conclusion, metabolic derangements begin early (Ͻ24 h) after TBI in the immature rat and are sustained for up to 7 days. Evaluation of early metabolic alterations after TBI could identify novel targets for neuroprotection in the developing brain.

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Section: Discussionmentioning

confidence: 99%

“…Evaluation of both NAA and lactate were made using creatine as a reference, as total creatine (creatine ϩ phosphocreatine) is relatively constant in the brain after injury (Yeo et al, 2006) and during rat brain development (Burri et al, 1990). At 4 h after TBI ( Fig.…”

Section: N-acetyl-aspartate and Lactate Relationshipmentioning

confidence: 99%

Early and Sustained Alterations in Cerebral Metabolism after Traumatic Brain Injury in Immature Rats

Casey

McKenna

Fiskum

et al. 2008

Journal of Neurotrauma

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“…In vitro MRS studies of NAA responses to osmotic stress-MRS has been reported to be an accurate method for measuring brain metabolite concentrations in vitro (Burri et al, 1990). These methods often employ extraction of solutes from tissues with perchloric acid, and subsequent analysis of the recovered metabolites by MRS. One study using MRS to detect metabolite concentrations in perchloric acid extracts from brain slices have shown a 60% decrease in NAA concentrations after hypo-osmotic shock (Bothwell et al, 2001).…”

Section: 31mentioning

confidence: 99%

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Moffett

Ross

Arun

et al. 2007

Progress in Neurobiology

1,230

1,126

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The brain is unique among organs in many respects, including its mechanisms of lipid synthesis and energy production. The nervous system-specific metabolite N-acetylaspartate (NAA), which is synthesized from aspartate and acetyl-coenzyme A in neurons, appears to be a key link in these distinct biochemical features of CNS metabolism. During early postnatal CNS development, the expression of lipogenic enzymes in oligodendrocytes, including the NAA-degrading enzyme aspartoacylase (ASPA), is increased along with increased NAA production in neurons. NAA is transported from neurons to the cytoplasm of oligodendrocytes, where ASPA cleaves the acetate moiety for use in fatty acid and steroid synthesis. The fatty acids and steroids produced then go on to be used as building blocks for myelin lipid synthesis. Mutations in the gene for ASPA result in the fatal leukodystrophy Canavan disease, for which there is currently no effective treatment. Once postnatal myelination is completed, NAA may continue to be involved in myelin lipid turnover in adults, but it also appears to adopt other roles, including a bioenergetic role in neuronal mitochondria. NAA and ATP metabolism appear to be linked indirectly, whereby acetylation of aspartate may facilitate its removal from neuronal mitochondria, thus favoring conversion of glutamate to alpha ketoglutarate which can enter the tricarboxylic acid cycle for energy production. In its role as a mechanism for enhancing mitochondrial energy production from glutamate, NAA is in a key position to act as a magnetic resonance spectroscopy marker for neuronal health, viability and number. Evidence suggests that NAA is a direct precursor for the enzymatic synthesis of the neuron specific dipeptide N-acetylaspartylglutamate, the most concentrated neuropeptide in the human brain. Other proposed roles for NAA include neuronal osmoregulation and axon-glial signaling. We propose that NAA may also be involved in brain nitrogen balance. Further research will be required to more fully understand the biochemical functions served by NAA in CNS development and activity, and additional functions are likely to be discovered.

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“…Like for lactate, with which it is in equilibrium though pyruvate, conflicting observations were reported for alanine concentrations in the developing rat brain (Bayer and McMurray, 1967;Burri et al, 1990;Tkáč et al, 2003). However, both in vivo and in vitro studies in mice demonstrated that cerebral alanine content is higher at birth and decreases during development (Kulak et al, 2010;Yao et al, 1999), reflecting the high protein turnover in the developing brain as result of cell proliferation and tissue expansion.…”

Section: Energy Metabolismmentioning

confidence: 99%