Metabolic fate of glucose in rats with traumatic brain injury and pyruvate or glucose treatments: A NMR spectroscopy study

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.

Pyruvate in reduced osmolarity oral rehydration salt corrected lactic acidosis in sever scald rats

“…Compared with them, pyruvate has multifactorial benefits because of its favorable properties associated with cellular function: enhancement of anoxia and/or hypoxia tolerance, antioxidative stress and anti-inflammation, and prevention of apoptosis in severe pathogenic insults. [3][4][5][6][7][8] Recently, compared with the bicarbonate-based ORS (WHO-ORS I, 331 mOsm/L), a novel pyruvate-based ORS (Pyr-ORS, pyruvate replaces equimolar bicarbonate in WHO-ORS I, 335 mOsm/L) showed its advantages. It enhanced intestinal absorption of sodium and water, improved visceral blood flow, and preserved multiple organs in rehydration of lethal shock in rodents.…”

Massive efflux of adenosine triphosphate into the extracellular space immediately after experimental traumatic brain injury

“…After 80 min of baseline sampling (collection of four 20-min fractions) both microdialysis probes were retracted by raising the micromanipulator until the probes were ~10 mm above the cortical surface. Sham injury or CCI injury was then induced, similar to what is described in our prior studies (21)(22)(23) but with reduced tissue compression to induce a milder injury. A 4-mm diameter flat-tipped impactor, which was angled 20˚ from vertical to be perpendicular to the dura mater at the injury site, was used to induce CCI centered at 3.0 mm posterior and 4.5 mm lateral relative to Bregma (20 psi, 2.37 m/sec, 1.5 mm tissue compression for 250 msec).…”

Uncovering temporally sensitive targeting motifs for traumatic brain injury via phage display

“…Pyruvate metabolism and TCA cycle, two pathways revealed by subsequent A2 target pathway analysis, work in tandem to regulate cerebral metabolism [49]. After TBI, these pathways are inhibited due to oxidative stress damage caused by mitochondrial dysfunction [50]. Ontological analysis revealed two individual components targeted by A2 that are implicated in these pathways and highly represented in the mass spectrometry data; succinate CoA ligase β and citrate synthase (CS) ( Table 3).…”