title: Cerebral glucose metabolism in an immature rat model of pediatric traumatic brain injury.
abstract: Altered cerebral metabolism and mitochondrial function have been identified in experimental and clinical studies of pediatric traumatic brain injury (TBI). Metabolic changes detected using (1)H (proton) magnetic resonance spectroscopy correlate with long-term outcomes in children after severe TBI. We previously identified early (4-h) and sustained (24-h and 7-day) abnormalities in brain metabolites after controlled cortical impact (CCI) in immature rats. The current study aimed to identify specific alterations of cerebral glucose metabolism at 24 h after TBI in immature rats. Rats (postnatal days 16-18) underwent CCI to the left parietal cortex. Sham rats underwent craniotomy only. Twenty-four hours after CCI, rats were injected (intraperitoneally) with [1,6-(13)C]glucose. Brains were removed, separated into hemispheres, and frozen. Metabolites were extracted with perchloric acid and analyzed using (1)H and (13)C-nuclear magnetic resonance spectroscopy. TBI resulted in decreases in N-acetylaspartate in both hemispheres, compared to sham contralateral. At 24 h after TBI, there was significant decrease in the incorporation of (13)C label into [3-(13)C]glutamate and [2-(13)C]glutamate in the injured brain. There were no differences in percent enrichment of [3-(13)C]glutamate, [4-(13)C]glutamate, [3-(13)C]glutamine, or [4-(13)C]glutamine. There was significantly lower percent enrichment of [2-(13)C]glutamate in both TBI sides and the sham craniotomy side, compared to sham contralateral. No differences were detected in enrichment of (13)C glucose label in [2-(13)C]glutamine, [2-(13)C]GABA (gamma-aminobutyric acid), [3-(13)C]GABA, or [4-(13)C]GABA, [3-(13)C]lactate, or [3-(13)C]alanine between groups. Results suggest that overall oxidative glucose metabolism in the immature brain recovers at 24 h after TBI. Specific reductions in [2-(13)C]glutamate could be the result of impairments in either neuronal or astrocytic metabolism. Future studies should aim to identify pathways leading to decreased metabolism and develop cell-selective "metabolic rescue."
authors.affiliation: 1 Department of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine , Baltimore, Maryland.
authors.forename: Courtney L
authors.initials: CL
authors.lastname: Robertson
authors.forename: Manda
authors.initials: M
authors.lastname: Saraswati
authors.forename: Susanna
authors.initials: S
authors.lastname: Scafidi
authors.forename: Gary
authors.initials: G
authors.lastname: Fiskum
authors.forename: Paula
authors.initials: P
authors.lastname: Casey
authors.forename: Mary C
authors.initials: MC
authors.lastname: McKenna
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005947:Glucose
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