Dynamic monitoring of cerebral metabolites during and after transient global ischemia in rats by quantitative proton NMR spectroscopy in vivo

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Abstract
Localized proton NMR spectroscopy was used to dynamically monitor alterations of cerebral metabolites before, during, and after a 10 min period of global forebrain ischemia in anesthetized rats. Metabolic assessment was based on user-independent determination of absolute brain concentrations at a nominal temporal resolution of 1.6 min. While the concentrations of N-acetyl aspartate (neuronal marker), creatines, cholines, and myo-inositol (glial marker) remained constant, ischemia induced a rapid decline of brain glucose. One hour after reperfusion, glucose recovered to 4.1± 2.2 mmol/kg wet weight significantly above the basal value of 2.3± 1.3 mmol/kg wet weight. Mirroring glucose depletion, lactate increased from 1.0±0.6 to 13.5±1.5 mmol/kg wet weight 10-15 min after the onset of ischemia. During reperfusion lactate clearance was characterized by a first-order rate constant of 0.03/min. The time courses of glucose and lactate reflect the rapid onset of anaerobic glycolysis during states of critically diminished blood flow. Assuming complete ischemia the production of lactate from glucose and cerebral glycogen stores yields a brain glycogen concentration of 4.7±0.9 mmol glycosyl unit/kg wet weight. Elevation of brain glucose during early reperfusion suggests a transient mismatch of glucose uptake and consumption during the first 1-2 hours post ischemia.