Effect of Ischemia and Reperfusion on λ of the Lumped Constant of the [<sup>14</sup>C]Deoxyglucose Technique

Greenberg, Joel; Hamar, J.; Welsh, Frank A.; Harris, Valerie; Reivich, Martin

doi:10.1038/jcbfm.1992.9

Cited by 15 publications

(3 citation statements)

References 28 publications

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“…The lumped constant is not likely to change during the experimental period, but it may vary between species and conditions 2 -22 - 23 and with age. 20 The lumped constant is generally broken into three sets of variables.…”

Section: Local Cerebral Glucose Utilization Modelmentioning

confidence: 99%

Cerebral glucose utilization and blood flow in adult spontaneously hypertensive rats.

et al. 1992

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Not only blood pressure but also behavioral activity, brain morphology, and cerebral ventricular size differ between young spontaneously hypertensive rats (SHR) and nonnotensive Wistar-Kyoto (WKY) rats. This suggests that cerebral blood flow and cerebral metabolism may vary between these two rat strains. To test this hypothesis, we measured local cerebral glucose utilization in 31 brain areas of 26-30 -week-old rats. Local cerebral blood flow was also assessed in these same areas. Cerebral glucose utilization was measured by the 2-deoxyglucose method; cerebral blood flow was determined by the iodoantipyrene method. In virtually all gray matter structures, the apparent rate of glucose utilization was lower in SHR than in nonnotensive WKY rats; the interstrain differences varied significantly among structures and were statistically significant (uncorrected t tests) in 14 of 28 gray matter areas. Local cerebral blood flow was fairly similar in the two rat strains. The coupling of blood flow to glucose utilization varied significantly among brain areas in nonnotensive WKY rats as well as in SHR. In a number of gray matter structures, the coupling of flow to metabolism differed between hypertensive and nonnotensive animals. These data suggest that for many brain areas, either glucose utilization or glucose partitioning differs between WKY rats and SHR. A number of years ago, Sokoloff and coworkers 2 developed the carbon-14-labeled 2-deoxyglucose (2DG) method of measuring glucose metabolism and, by use of quantitative autoradiography, assessed local cerebral glucose utilization (LCGU) in more than 30 areas of the rat brain. Subsequently, the 2DG technique has been used extensively to measure changes and differences in brain metabolism in a variety of studies and has provided considerable information on local alterations in cerebral activity. Using the 2DG technique, Kadekaro et al 3 determined that LCGU was very similar in 41 of 44 brain areas of 11-12-week-old spontaneously hypertensive rats (SHR) and their normotensive, genetically related control, the Wistar-Kyoto (WKY) rat. This suggested that metabolism is relatively normal in the brain of juvenile SHR. Differences in mean arterial blood pres- sure (MABP) and behavior 4 -3 as well as in brain weight and structure and ventricular size 6 -9 between SHR and WKY rats, however, have been reported at this and other stages of development.In view of these physiological, behavioral, and morphological observations, we have postulated that cerebral glucose utilization is altered in adult SHR and have tested this hypothesis by measuring LCGU in 26-30-week-old SHR and WKY rats by the 2DG technique of Sokoloff et al. 2 In addition, because of the purported coupling between LCGU and local cerebral blood flow (LCBF) and of the possible change in this coupling in chronically hypertensive animals, LCBF was determined in age-matched SHR and WKY rats by the radiolabeled iodoantipyrine (IAP) technique of Sakurada et al. 10 In both the LCGU and the LCBF experiments, quantitative autor...

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Section: Local Cerebral Glucose Utilization Modelmentioning

confidence: 99%

Cerebral glucose utilization and blood flow in adult spontaneously hypertensive rats.

et al. 1992

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“…Thus it cannot be excluded that changed expression of glucose transporters, shown to occur following diffuse brain injury and hypoxia-ischemia in the immature rat brain (Hamlin et al, 2001;Vannucci et al, 1998), influence transport of glucose and thus lCMR Glc calculations, at least at the 12-h post-injury time point. Previous studies demonstrated a changed l of the LC following both hypo-and hyperglycemia (Crane et al, 1983;Mori et al, 1989), and the LC was also changed following cerebral ischemia associated with a critically reduced cerebral blood flow (Greenberg et al, 1992;Nakai et al, 1987b). Finally, the release of lysosomal acid hydrolases after brain injury might alter the value of F by causing hydrolysis of 2-deoxyglucose 6-phosphate (Nakai et al, 1987a).…”

Section: The Lumped Constant May Be Altered Early Post-injurymentioning

confidence: 98%

“…where l is the ratio of the distribution volumes of DG and glucose in the tissue; F is the fraction of glucose that, once phosphorylated, continues down the glycolytic pathway; and V m , K m , V* m , and K* m are the Michaelis-Menten kinetic constants of hexokinase for glucose and DG, respectively (Graham et al, 2002;Greenberg et al, 1992;Sokoloff et al, 1977;Wienhard, 2002;Wu et al, 2003). A ''pooled'' LC value, calculated from brain areas remote from a contusion and different from the LC of healthy control subjects, was used for the estimation of lCMR Glc following human TBI (Hattori et al, 2003).…”

Section: The Lumped Constant May Be Altered Early Post-injurymentioning

confidence: 99%

Increased Cerebral Uptake of [¹⁸F]Fluoro-Deoxyglucose but not [1-¹⁴C]Glucose Early following Traumatic Brain Injury in Rats

Marklund

Sihver

Hovda

et al. 2009

Journal of Neurotrauma

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Following experimental and clinical traumatic brain injury (TBI), the local cerebral metabolic rate of glucose (lCMR(Glc)) is commonly estimated using the 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) method. The adequate estimation of lCMR(Glc) using FDG requires a correction factor, the lumped constant (LC), to convert FDG net uptake into lCMR(Glc). The LC, and thus lCMR(Glc) calculations, require a steady-state that may be disrupted following TBI. In the present report, we hypothesized that [1-(14)C]glucose uptake would accurately reflect glucose dynamics early post-injury, and was compared to the regional uptake of FDG in 44 rats subjected to moderate (2.4-2.6 atm) lateral fluid percussion brain injury (FPI) or sham injury. Cortical energy state and adenylate (ATP, ADP, and AMP) levels were also measured. Early (7-42 min) after FPI, FDG uptake was increased in the ipsilateral cortex and hippocampus (p < 0.05). In contrast, no change in [1-(14)C]glucose uptake (7 and 17 min post-injury) or cortical adenylate content (42 min post-injury) was observed. At 12 h following FPI, the ipsilateral FDG and [1-(14)C]glucose uptake were decreased in the cortex and hippocampus, and the ipsilateral cortical ATP concentration was decreased in comparison to sham-injured controls (p < 0.05). Under the present experimental conditions, the rate of cerebral uptake of FDG and of [1-(14)C]glucose differed, and indicated that following TBI, regional changes in the LC may occur in the immediate, but not in the late, post-injury phase. These results should be considered when interpreting results obtained using FDG for the estimation of lCMR(Glc) early following experimental TBI.

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Cerebral transport and metabolism of 1‐¹¹C‐D‐glucose during stepped hypoglycemia

Powers

Dagogo‐Jack

Markham

et al. 1995

Annals of Neurology

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Attempts to measure blood-to-brain glucose transport and cerebral glucose metabolism with 11C-glucose have been hampered by methods that require jugular venous sampling or do not adequately account for the efflux of labeled metabolites from the brain. We performed eight positron emission tomography studies with 1-11C-D-glucose in macaques at arterial plasma glucose concentrations of 8.43 to 1.51 mumol ml-1 (152-27 mg dl-1) using a model that includes a fourth rate constant to account for regional egress of all 11C-metabolites. Values for blood-to-brain glucose influx, cerebral glucose metabolism, and brain free glucose concentration agreed closely with values obtained in mammals by other investigators. Values for net extraction fraction corresponded closely to simultaneously measured arteriovenous values. We demonstrated that utilization of a model that includes a fourth rate constant to account for regional egress of all 11C-metabolites with positron emission tomography and 1-11C-D-glucose provides accurate measurements of blood-to-brain glucose transport and cerebral glucose metabolism in vivo without need for jugular venous sampling, even under conditions of severe hypoglycemia.

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Effect of Ischemia and Reperfusion on λ of the Lumped Constant of the [¹⁴C]Deoxyglucose Technique

Cited by 15 publications

References 28 publications

Cerebral glucose utilization and blood flow in adult spontaneously hypertensive rats.

Cerebral glucose utilization and blood flow in adult spontaneously hypertensive rats.

Increased Cerebral Uptake of [¹⁸F]Fluoro-Deoxyglucose but not [1-¹⁴C]Glucose Early following Traumatic Brain Injury in Rats

Cerebral transport and metabolism of 1‐¹¹C‐D‐glucose during stepped hypoglycemia

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Effect of Ischemia and Reperfusion on λ of the Lumped Constant of the [14C]Deoxyglucose Technique

Cited by 15 publications

References 28 publications

Cerebral glucose utilization and blood flow in adult spontaneously hypertensive rats.

Cerebral glucose utilization and blood flow in adult spontaneously hypertensive rats.

Increased Cerebral Uptake of [18F]Fluoro-Deoxyglucose but not [1-14C]Glucose Early following Traumatic Brain Injury in Rats

Cerebral transport and metabolism of 1‐11C‐D‐glucose during stepped hypoglycemia

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Resources

About

Effect of Ischemia and Reperfusion on λ of the Lumped Constant of the [¹⁴C]Deoxyglucose Technique

Increased Cerebral Uptake of [¹⁸F]Fluoro-Deoxyglucose but not [1-¹⁴C]Glucose Early following Traumatic Brain Injury in Rats

Cerebral transport and metabolism of 1‐¹¹C‐D‐glucose during stepped hypoglycemia