Simultaneous Measurement of Glucose Blood–Brain Transport Constants and Metabolic Rate in Rat Brain using in-vivo¹H MRS

Abstract

Cerebral glucose consumption and glucose transport across the blood-brain barrier are crucial to brain function since glucose is the major energy fuel for supporting intense electrophysiological activity associated with neuronal firing and signaling. Therefore, the development of noninvasive methods to measure the cerebral metabolic rate of glucose (CMR glc ) and glucose transport constants (K T : half-saturation constant; T max : maximum transport rate) are of importance for understanding glucose transport mechanism and neuroenergetics under various physiological and pathological conditions. In this study, a novel approach able to simultaneously measure CMR glc , K T , and T max via monitoring the dynamic glucose concentration changes in the brain tissue using in-vivo 1 H magnetic resonance spectroscopy (MRS) and in plasma after a brief glucose infusion was proposed and tested using an animal model. The values of CMR glc , T max , and K T were determined to be 0.44 ± 0.17 lmol/g per minute, 1.35 ± 0.47 lmol/g per minute, and 13.4 ± 6.8 mmol/L in the rat brain anesthetized with 2% isoflurane. The Monte-Carlo simulations suggest that the measurements of CMR glc and T max are more reliable than that of K T . The overall results indicate that the new approach is robust and reliable for in-vivo measurements of both brain glucose metabolic rate and transport constants, and has potential for human application.

MRS glucose mapping and PET joining forces: re‐evaluation of the lumped constant in the rat brain under isoflurane anaesthesia

“…; Du et al . ). As this assumption may result in underestimating T max from PET data, we simulated the effect of T max on LC isoflurane (Fig.…”

“…Both T max and T max / CMR glc reported in this study were in good agreement with previous determinations in the rat brain under isoflurane anaesthesia by dynamic measurement of brain and plasma glucose concentrations (Du et al . ; Duarte and Gruetter ).…”

“…; Du et al . ; Duarte and Gruetter ). PET with FDG offers information on the mechanistic basis of CMR glc and is a relatively uncomplicated method, leading to its widespread employment.…”

“…Notwithstanding its great merits, particularly allowing to determine fluxes through a large number of metabolic reactions, 13 C MRS faces limitations regarding spatial resolution. Although 1 H MRS has been mostly restricted to provide information on the ratio of glucose transport over consumption, recent studies have been designed to quantify both transport kinetics and the cerebral metabolic rate of glucose (CMR glc ) from the dynamic measurement of brain glucose concentration upon plasma glucose variation (Gruetter et al 1996;Shestov et al 2011;Du et al 2012;Duarte and Gruetter 2012a). PET with FDG offers information on the mechanistic basis of CMR glc and is a relatively uncomplicated method, leading to its widespread employment.…”

In vivo continuous and simultaneous monitoring of brain energy substrates with a multiplex amperometric enzyme-based biosensor device

“…Despite accounting for only 2% of the total body mass, it requires up to 25% of the total glucose consumption (Brady et al, 2006;Genc et al, 2011). Its high requirements are dependent on a continuous flow of energy substrates from the circulating blood (Du et al, 2012), and the activation of discrete brain areas is directly related to increases in Advances in the technology for monitoring neuroenergetics have provided evidence that challenges this view (Drevets et al, 2002;El Hage et al, 2011;Erlichman et al, 2008;Hertz et al, 2007). Increases in blood flow and brain glucose utilization, in response to increases in energy requirements, are not matched by parallel increases in oxygen consumption, necessary for full glucose metabolism dependency (Fillenz and Lowry, 1998;Hertz et al, 2007;Kiyatkin and Lenoir, 2012;Leegsma-Vogt et al, 2003;Lowry et al, 1998a;Lowry and Fillenz, 1997).…”