Upregulation of Pentose Phosphate Pathway and Preservation of Tricarboxylic Acid Cycle Flux after Experimental Brain Injury
- 1 October 2005
- journal article
- research article
- Published by Mary Ann Liebert Inc in Journal of Neurotrauma
- Vol. 22 (10) , 1052-1065
- https://doi.org/10.1089/neu.2005.22.1052
Abstract
The metabolic fate of [1,2 13C]–labeled glucose was determined in male control and unilateral controlled cortical impact (CCI) injured rats at 3.5 and 24 h after surgery. The concentration of 13C-labeled glucose, lactate, glutamate and glutamine were measured in the injured and contralateral cortex. CCI animals showed a 145% increase in 13C lactate in the injured cortex at 3.5 h, but not at 24 h after injury, indicating increased glycolysis in neurons and/or astrocytes ipsilateral to CCI. Total levels of 13C glutamate in cortical tissue extracts did not differ between groups. However, 13C glutamine increased by 40% in the left and 98% in the right cortex at 3.5 h after injury, most likely resulting from an increase in astrocytic metabolism of glutamate. Levels of 13C incorporation into the glutamine isotopomers had returned to control levels by 24 h after CCI. The singlet to doublet ratio of the lactate C3 resonances was calculated to estimate the flux of glucose through the pentose phosphate pathway (PPP). CCI resulted in bilateral increases (9–12%) in the oxidation of glucose via the PPP, with the largest increase occurring at 24 h. Since an increase in PPP activity is associated with NADPH generation, the data suggest that there was an increasing need for reducing equivalents after CCI. Furthermore, 13C was incorporated into glutamate and glutamine isotopomers associated with multiple turns of the tricarboxylic acid (TCA) cycle, indicating that oxidative phosphorylation of glucose was maintained in the injured cortex at 3.5 and 24 h after a moderate to severe CCI injury.Keywords
This publication has 87 references indexed in Scilit:
- Glutamatergic Neurotransmission and Neuronal Glucose Oxidation are Coupled during Intense Neuronal ActivationJournal of Cerebral Blood Flow & Metabolism, 2004
- Metabolism of [1-13C]glucose and [2-13C]acetate in the hypoxic rat brainNeurochemistry International, 2001
- Metabolism of (1-13C) glucose and (2-13C, 2-2H3) acetate in the neuronal and glial compartments of the adult rat brain as detected by {13C, 2H} NMR spectroscopyNeurochemistry International, 2000
- Oxidative stress-induced metabolic alterations in rat brain astrocytes studied by multinuclear NMR spectroscopyJournal of Neuroscience Research, 1999
- In Vivo Injection of [1-13C]Glucose and [1,2-13C]Acetate Combined with Ex Vivo13C Nuclear Magnetic Resonance Spectroscopy: A Novel Approach to the Study of Middle Cerebral Artery Occlusion in the RatJournal of Cerebral Blood Flow & Metabolism, 1998
- Metabolic Precursors and Compartmentation of Cerebral GABA in Vigabatrin‐Treated RatsJournal of Neurochemistry, 1996
- Assessment of the Role of the Glutathione and Pentose Phosphate Pathways in the Protection of Primary Cerebrocortical Cultures from Oxidative StressJournal of Neurochemistry, 1996
- Cerebral Metabolic Compartmentation as Revealed by Nuclear Magnetic Resonance Analysis of D‐[1‐13C]Glucose MetabolismJournal of Neurochemistry, 1993
- Hypermetabolic state following experimental head injuryNeurosurgical Review, 1989
- The Rate of Utilization of Glucose Via Hexosemonophosphate Shunt in BrainJournal of Neurochemistry, 1983