title: 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 [1,213C] glucose for 68 min13C 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 [413C] 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 of13C 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.
authors.affiliation: Brain Injury Research Center, Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, Box 956901, CA, USA. Electronic address: sijyou.katsunori@nihon-u.ac.jp.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Shijo
authors.affiliation: Brain Injury Research Center, Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, Box 956901, CA, USA. Electronic address: rsutton@ucla.edu.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Sutton
authors.affiliation: Brain Injury Research Center, Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, Box 956901, CA, USA. Electronic address: sghavim@mednet.ucla.edu.
authors.forename: Sima S
authors.initials: SS
authors.lastname: Ghavim
authors.affiliation: Brain Injury Research Center, Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, Box 956901, CA, USA. Electronic address: ngharris@ucla.edu.
authors.forename: Neil G
authors.initials: NG
authors.lastname: Harris
authors.affiliation: Department of Radiology, Loma Linda University School of Medicine, Loma Linda, CA, USA. Electronic address: bbartnik@llu.edu.
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Bartnik-Olson
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D000070642:Brain Injuries, Traumatic / Q000378:metabolism*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D019289:Pyruvic Acid / Q000378:metabolism*; D017207:Rats, Sprague-Dawley
chemical_list: D005973:Glutamine; D018698:Glutamic Acid; D019289:Pyruvic Acid; D005947:Glucose
keywords: Controlled cortical impact; Ethyl pyruvate; Glucose; Oxidative metabolism; Pentose phosphate pathway; Sodium pyruvate