TY - JOUR
T1 - Cerebral glucose metabolism in an immature rat model of pediatric traumatic brain injury
AU - Robertson, Courtney L.
AU - Saraswati, Manda
AU - Scafidi, Susanna
AU - Fiskum, Gary
AU - Casey, Paula
AU - McKenna, Mary C.
PY - 2013/12/15
Y1 - 2013/12/15
N2 - Altered cerebral metabolism and mitochondrial function have been identified in experimental and clinical studies of pediatric traumatic brain injury (TBI). Metabolic changes detected using 1H (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 [1,6-13C]glucose. Brains were removed, separated into hemispheres, and frozen. Metabolites were extracted with perchloric acid and analyzed using 1H and 13C-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 13C label into [3-13C]glutamate and [2-13C]glutamate in the injured brain. There were no differences in percent enrichment of [3-13C]glutamate, [4-13C]glutamate, [3-13C]glutamine, or [4-13C]glutamine. There was significantly lower percent enrichment of [2-13C]glutamate in both TBI sides and the sham craniotomy side, compared to sham contralateral. No differences were detected in enrichment of 13C glucose label in [2-13C]glutamine, [2-13C]GABA (gamma-aminobutyric acid), [3-13C]GABA, or [4-13C]GABA, [3-13C]lactate, or [3-13C]alanine between groups. Results suggest that overall oxidative glucose metabolism in the immature brain recovers at 24 h after TBI. Specific reductions in [2-13C]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."
AB - Altered cerebral metabolism and mitochondrial function have been identified in experimental and clinical studies of pediatric traumatic brain injury (TBI). Metabolic changes detected using 1H (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 [1,6-13C]glucose. Brains were removed, separated into hemispheres, and frozen. Metabolites were extracted with perchloric acid and analyzed using 1H and 13C-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 13C label into [3-13C]glutamate and [2-13C]glutamate in the injured brain. There were no differences in percent enrichment of [3-13C]glutamate, [4-13C]glutamate, [3-13C]glutamine, or [4-13C]glutamine. There was significantly lower percent enrichment of [2-13C]glutamate in both TBI sides and the sham craniotomy side, compared to sham contralateral. No differences were detected in enrichment of 13C glucose label in [2-13C]glutamine, [2-13C]GABA (gamma-aminobutyric acid), [3-13C]GABA, or [4-13C]GABA, [3-13C]lactate, or [3-13C]alanine between groups. Results suggest that overall oxidative glucose metabolism in the immature brain recovers at 24 h after TBI. Specific reductions in [2-13C]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."
KW - NMR spectroscopy
KW - developmental brain injury
KW - metabolism
KW - mitochondria
KW - trauma
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U2 - 10.1089/neu.2013.3007
DO - 10.1089/neu.2013.3007
M3 - Article
C2 - 24032394
AN - SCOPUS:84890480748
SN - 0897-7151
VL - 30
SP - 2066
EP - 2072
JO - Journal of neurotrauma
JF - Journal of neurotrauma
IS - 24
ER -