Regional Cerebral Glucose Utilization in the Immature Rat: Effect of Hypoxia-Ischemia

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Abstract
The 2-deoxy-[14C]-glucose (2-DG) method of Sokoloff was used to assess regional cerebral glucose utilization (CGU) in the immature rat. The 7-d postnatal rats received 2.5 Alt+0181Ci 2-DG subcutaneously, after which blood was collected for measurement of plasma glucose and 2-DG activity at intervals up to 90 min. The brains of the 90-min rat pups either were frozen for analysis of glucose concentration and chromatographic separation of 2-DG and 2-DG-6-phosphate or for [14C]-autoradiography. A lumped constant of 0.55 was calculated from plasma and brain glucose levels of 6.4 and 1.62 mmol/L.kg, respectively. Of the [14C] activity in brain, 75.6% was in the 2-DG-6-phosphate fraction; this percent was substituted for Kl*, K2*, and K3* in the Sokoloff equation. Cerebral hemispheric CGU (n = 6) averaged 11.4 ± 1.5 Alt+0181mol/100 g/min, 1/10 the value of adult rat brain. Rates in 16 brain structures (n = 10) ranged from 7.8 (frontal white matter) to 16.9 (cerebellum) Alt+0181mol/100 g/min. During hypoxiaischemia (unilateral common carotid artery ligation combined with exposure to 8% oxygen), the lumped constant increased to 1.04, and 99% of 2-DG was converted to 2-DG-6-phosphate. Increases in CGU occurred in all eight structures of the cerebral hemisphere ipsilateral to the carotid artery occlusion (n = 9), ranging from 287% (frontal white matter) to 445% (striatum) of control values (p < 0.05). Relatively comparable elevations in CGU (234-435% of control) occurred in the contralateral cerebral hemisphere, which were not significantly different from those of the ipsilateral hemisphere. The relatively proportionate increases in regional CGU of the two cerebral hemispheres, only one of which sustains tissue injury, suggest interhemispheric differences in the extent to which glucose is metabolized via anaerobic glycolysis to maintain cellular energy production. The investigation demonstrates the feasibility of measuring regional CGU in the small laboratory animal, which is applicable to a variety of physiologic and pathologic situations.

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