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Review
. 2013 Oct 4:5:8.
doi: 10.3389/fnene.2013.00008.

Insights into the metabolic response to traumatic brain injury as revealed by (13)C NMR spectroscopy

Brenda L Bartnik-Olson  1 , Neil G Harris, Katsunori Shijo, Richard L Sutton
Affiliations
Review

Insights into the metabolic response to traumatic brain injury as revealed by (13)C NMR spectroscopy

Brenda L Bartnik-Olson et al. Front Neuroenergetics. .

Abstract

The present review highlights critical issues related to cerebral metabolism following traumatic brain injury (TBI) and the use of (13)C labeled substrates and nuclear magnetic resonance (NMR) spectroscopy to study these changes. First we address some pathophysiologic factors contributing to metabolic dysfunction following TBI. We then examine how (13)C NMR spectroscopy strategies have been used to investigate energy metabolism, neurotransmission, the intracellular redox state, and neuroglial compartmentation following injury. (13)C NMR spectroscopy studies of brain extracts from animal models of TBI have revealed enhanced glycolytic production of lactate, evidence of pentose phosphate pathway (PPP) activation, and alterations in neuronal and astrocyte oxidative metabolism that are dependent on injury severity. Differential incorporation of label into glutamate and glutamine from (13)C labeled glucose or acetate also suggest TBI-induced adaptations to the glutamate-glutamine cycle.

Keywords: acetate; glucose; glutamate-glutamine cycle; magnetic resonance spectroscopy; neuroglial compartmentation; oxidative metabolism; pentose phosphate pathway.

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Figures

Figure 1
Figure 1
Simplified illustration of the metabolic response to TBI as determined by 13C NMR spectroscopy using [1, 2 13C2] glucose. TBI-induced ion fluxes and neurotransmitter release can increase anaerobic metabolism and initiate an injury cascade including increased oxidative/nitrosative stress, PARP-1 activation, and NAD+ and/or NAPD+ reductions. These in turn are thought to result in the activation (+) or inhibition (−) of enzymes contributing to the metabolic response to TBI (see text). Using [1, 2 13C2] glucose as a precursor, 13C NMR spectroscopy can be used to measure increases (↑) or decreases (↓) in glycolysis, the PPP, oxidative metabolism in the TCA cycle, and the pyruvate recycling system by monitoring the production of [2, 3 13C2] lactate, [2 13C] lactate, and [4, 5 13C2] glutamate and [4 13C] glutamate.
Figure 2
Figure 2
Simplified illustration of changes in neuroglial metabolic coupling following FPI as determined using 13C labeled glucose and acetate. Findings show reduced (−) glucose metabolism in both neuron and astrocyte metabolic compartments, possibly due to reduced activity of GAPDH and/or PDH. The capacity for oxidative metabolism was retained (+) in the astrocyte compartment as 13C labeling was detected in glutamine isotopomers resulting from acetate metabolism via the TCA cycle and PC. Labeling of glutamate from 13C acetate indicates continued activity (+) of the glutamate-glutamine cycle and phosphate activated glutaminase (PAG). These findings could be interpreted to mean that astrocytes have a supportive metabolic role to neurons following TBI.
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