Metabolism of [1-13C]glucose and [2-13C]acetate in the hypoxic rat brain

The effects of hypoxia on the metabolism of the central nervous system were investigated in rats submitted to a low oxygen atmosphere (8% O-2; 92% N-2). [1-C-13]glucose and [2-C-13]acetate were used as substrates, this latter being preferentially metabolized by glial cells. After l-h substrate infusion, the incorporation of C-13 in brain metabolites was determined by NMR spectroscopy. Under hypoxia, an important hyperglycemia was noted. As a consequence, when using labeled glucose, the specific enrichment of brain glucose Cl was lower (48.2 +/- 5.1%) than under normoxia (66.9 +/- 2.5%). However, relative to this specific enrichment, the C-13 incorporation in amino acids was increased under hypoxia. This suggested primarily a decreased exchange between blood and brain lactate. The glutamate C2/C4 enrichment ratio was higher under hypoxia (0.62 +/- 0.01) than normoxia (0.51 +/- 0.06), indicating a lower glutamate turnover relative to the neuronal TCA cycle activity. The glutamine C2/C4 enrichment ratio was also higher under hypoxia (0.87 +/- 0.07 instead of 0.65 +/- 0.11), indicating a new balance in the contributions of different carbon sources at the acetyl-CoA level. When using [2-C-13]acetate as substrate, no difference in glutamine enrichment appeared under hypoxia, whereas a significant decrease in glutamate, aspartate, alanine and lactate enrichments was noted. This indicated a lower trafficking between astrocytes and neurons and a reduced tricarboxylic acid cycle intermediate recycling of pyruvate. (C) 2001 Elsevier Science Ltd. All rights reserved.