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

Abstract

ABSTRACT. The 2-deo~y-['~C]-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 pCi 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 ['4C]-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 [I4C] 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 wmo1/100 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) pmo1/100 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. (Pediatr Res 26: 208-214,1989) Abbreviations CGU, cerebral glucose utilization rCGU, regional CGU 2-DG, 2-deoxyglucose 2-DG-6-P, 2-deoxyglucose-6-phosphate s.c., ~ubcutaneous LC, lumped constant -P, high-energy phosphate bond The 2-DG technique, as originally developed by Sokoloff et al. (I), has become an established procedure to measure rCGU in adult animals. The method has been used in numerous species under a variety of physiologic and pathologic situations (2). Furthermore, the method provides the theoretical and practical basis for the measurement of rCGU in humans, including infants and children, using positron emission tomography (3, 4). Although rCGU has been determined in large perinatal animals (5-7), a systematic investigation of its applicability to the small laboratory animal has yet to be accomplished. We here describe a feasibility study to measure rCGU, using 2-DG, in the immature rat; and we have used the technique to ascertain the nature and extent of alterations in regional...

Differential Proteomics of the Cerebral Cortex of Juvenile, Adult and Aged Rats: An Ontogenetic Study

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Transient Rise of Glucose Uptake in the Fetal Rat Brain after Brief Episodes of Intrauterine Ischemia

“…This phenomenon has been attributed to an accelerated rate of glycolysis. An increase in cerebral glucose utilization in the imma ture rat after common carotic artery ligation combined with exposure to low oxygen was also demonstrated [34],…”

Evolution of Brain Injury After Transient Middle Cerebral Artery Occlusion in Neonatal Rats

“…Hypoxia plus ischemia, however, produces unilateral injury ipsilateral to the carotid artery ligation. 2,11,19,20 Because both a hypoxic episode and permanent common carotid artery (CCA) ligation are required to produce CNS injury, this model does not mimic the pathophysiology of transient obstruction of CBF seen in human neonates. 3 Reperfusion/reoxygenation after an ischemic episode can significantly exacerbate injury to brains of adults, as was demonstrated with the use of rodent models of focal permanent and transient cerebral ischemia (see References 21 and 22 for review).…”

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