Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jan;102:66-78.
doi: 10.1016/j.neuint.2016.11.014. Epub 2016 Dec 3.

Metabolic Fate of Glucose in Rats With Traumatic Brain Injury and Pyruvate or Glucose Treatments: A NMR Spectroscopy Study

Affiliations
Free PMC article

Metabolic Fate of Glucose in Rats With Traumatic Brain Injury and Pyruvate or Glucose Treatments: A NMR Spectroscopy Study

Katsunori Shijo et al. Neurochem Int. .
Free PMC article

Abstract

Administration of sodium pyruvate (SP; 9.08 μmol/kg, i.p.), ethyl pyruvate (EP; 0.34 μmol/kg, i.p.) or glucose (GLC; 11.1 μmol/kg, i.p.) to rats after unilateral controlled cortical impact (CCI) injury has been reported to reduce neuronal loss and improve cerebral metabolism. In the present study these doses of each fuel or 8% saline (SAL; 5.47 nmoles/kg) were administered immediately and at 1, 3, 6 and 23 h post-CCI. At 24 h all CCI groups and non-treated Sham injury controls were infused with [1,2 13C] glucose for 68 min 13C nuclear magnetic resonance (NMR) spectra were obtained from cortex + hippocampus tissues from left (injured) and right (contralateral) hemispheres. All three fuels increased lactate labeling to a similar degree in the injured hemisphere. The amount of lactate labeled via the pentose phosphate and pyruvate recycling (PPP + PR) pathway increased in CCI-SAL and was not improved by SP, EP, and GLC treatments. Oxidative metabolism, as assessed by glutamate labeling, was reduced in CCI-SAL animals. The greatest improvement in oxidative metabolism was observed in animals treated with SP and fewer improvements after EP or GLC treatments. Compared to SAL, all three fuels restored glutamate and glutamine labeling via pyruvate carboxylase (PC), suggesting improved astrocyte metabolism following fuel treatment. Only SP treatments restored the amount of [4 13C] glutamate labeled by the PPP + PR pathway to sham levels. Milder injury effects in the contralateral hemisphere appear normalized by either SP or EP treatments, as increases in the total pool of 13C lactate and labeling of lactate in glycolysis, or decreases in the ratio of PC/PDH labeling of glutamine, were found only for CCI-SAL and CCI-GLC groups compared to Sham. The doses of SP, EP and GLC examined in this study all enhanced lactate labeling and restored astrocyte-specific PC activity but differentially affected neuronal metabolism after CCI injury. The restoration of astrocyte metabolism by all three fuel treatments may partially underlie their abilities to improve cerebral glucose utilization and to reduce neuronal loss following CCI injury.

Keywords: Controlled cortical impact; Ethyl pyruvate; Glucose; Oxidative metabolism; Pentose phosphate pathway; Sodium pyruvate.

Figures

Fig. 1
Fig. 1
Timeline of post-surgical experimental procedures. Intraperitoneal injections of SAL, SP, EP or GLC were administered at 0, 1, 3, 6 and 23 h post-CCI injury. [1,2 13C2] labeled glucose was infused for 68 min starting at 24 h after CCI-injury. Arterial blood samples were taken prior to and at 15 and 67 min after the infusion of [1,2 13C2] glucose. CCI, controlled cortical impact; EP, ethyl pyruvate; GLC, glucose; SAL, saline; SP, sodium pyruvate.
Fig. 2
Fig. 2
13C labeling scheme following an infusion of [1,2 13C2] glucose. Black circles denote the possible position of 13C labeling on carbon backbones during metabolism. The isotopomers resulting from metabolism through glycolysis, the oxidative branch of the PPP, the first and second turns of the TCA cycle, and pyruvate recycling are shown. Gln, glutamine; Glu, glutamate; ME, malic enzyme; PC, pyruvate carboxylase; PDH, pyruvate dehydrogenase; PEPCK, phosphoenolpyruvate carboxykinase; PK, pyruvate kinase; PPP, pentose phosphate pathway; TCA, tricarboxylic acid cycle.
Fig. 3
Fig. 3
The total amount (nmol/mg protein) of 13C labeled glucose, lactate, glutamate, glutamine, GABA, and aspartate metabolite pools of the left (injured) cortex + hippocampus samples. CCI, controlled cortical impact; EP, ethyl pyruvate; GLC, glucose; SAL, saline; SP, sodium pyruvate. All values are expressed as mean ± SEM. *p < 0.05 versus Sham; ˆ p < 0.05 versus CCI-SAL; ŧ p < 0.05 versus CCI-SP using one-way ANOVA with Bonferroni post-hoc.
Fig. 4
Fig. 4
The overall changes in metabolite labeling in the first turn of the TCA cycle and the relative incorporation of 13C label via different metabolic pathways in the injured cortex + hippocampus of CCI-injured animals following SAL or fuel treatment compared to Sham injury non-treated controls. In the SAL treated CCI-injured animals oxidative metabolism via both PC and PDH was reduced resulting in reduced 13C labeling of glutamate and glutamine (red arrows). In addition, the relative contribution of the PPP + PR pathway to lactate labeling was increased (red arrow) although this did not significantly increase the 13C lactate pool compared to Sham-controls. Following SP treatment, CCI-injured animals had increased lactate labeling via glycolysis and the PPP + PR pathway (red arrows). Glutamate and glutamine labeling via PDH and PC was similar to Sham-controls (green arrows) indicating improved neuronal and astrocyte metabolism compared to SAL. Similar to the SP group, EP treatment results in an increase in lactate labeling via glycolysis and the PPP + PR pathway (red arrows). However, oxidative metabolism via PDH was reduced (red arrows). In contrast, glutamate and glutamine labeling via PC was similar to Sham-controls (green arrow) suggesting improved astrocyte metabolism. With GLC treatment, 13C label incorporation into lactate via the various metabolic pathways (red arrows) was similar to the pyruvate treatments. Oxidative metabolism via PDH resulted in reduced labeling of glutamate (red arrows), however labeling of glutamine via PC was restored with GLC treatment (green arrows). Compared to SAL, the restoration of astrocyte-specific PC metabolism by SP, EP, and GLC treatment may underlie their abilities to improve cerebral glucose utilization and reduce neuronal loss following CCI injury. CCI, controlled cortical impact; EP, ethyl pyruvate; GLC, glucose; Lac, lactate; PC, pyruvate carboxylase; PDH, pyruvate dehydrogenase; PPP, pentose phosphate pathway; PR, pyruvate recycling; SAL, saline; SP, sodium pyruvate; TCA, tricarboxylic acid cycle.

Similar articles

See all similar articles

Cited by 1 article

Publication types

Feedback