Abstract
Brain growth across childhood is a dynamic process associated with specific energy requirements. A disproportionately higher rate of glucose utilization (CMRglucose) compared with oxygen consumption (CMRO2) was documented in children's brain and suggestive of non-oxidative metabolism of glucose. Several candidate metabolic pathways may explain the CMRglucose-CMRO2 mismatch, and lactate production is considered a major contender. The ~33% excess CMRglucose equals 0.18 μmol glucose/g/min and predicts lactate release of 0.36 μmol/g/min. To validate such scenario, we measured the brain lactate concentration ([Lac]) in 65 children to determine if indeed lactate accumulates and is high enough to (1) account for the glucose consumed in excess of oxygen and (2) support a high rate of lactate efflux from the young brain. Across childhood, brain [Lac] was lower than predicted, and below the range for adult brain. In addition, we re-calculated the CMRglucose-CMRO2 mismatch itself by using updated lumped constant values. The calculated cerebral metabolic rate of lactate indicated a net influx of 0.04 μmol/g/min, or in terms of CMRglucose, of 0.02 μmol glucose/g/min. Accumulation of [Lac] and calculated efflux of lactate from brain are not consistent with the increase in non-oxidative metabolism of glucose. In addition, the value for the lumped constant for [18F]fluorodeoxyglucose has a high impact on calculated CMRglucose and use of updated values alters or eliminates the CMRglucose-CMRO2 mismatch in developing brain. We conclude that the presently-accepted notion of non-oxidative metabolism of glucose during childhood must be revisited and deserves further investigations.
Highlights
Understanding the metabolic needs of the developing brain is essential for maintaining brain health across childhood and during adolescence
In order to assess spectral quality the 1H magnetic resonance spectroscopy (MRS) spectra were checked for poor signal-to-noise ratio (SNR), spectral line width via full width at half maximum (FWHM) and baseline fluctuations estimated from linear combination of model (LCModel) analysis (Provencher, 2001), and 13 spectra were excluded
The Cramer–Rao lower bounds (CRLBs) which are the standard error estimates expressed in percent of the estimated concentrations (%SD) calculated by LCModel analysis (Provencher, 2001) for [total creatine (tCr)], [tNAA], [total choline (tCh)] were 2–5%SD; and CRLB’s for [tGlx] were 8–14%SD
Summary
Understanding the metabolic needs of the developing brain is essential for maintaining brain health across childhood and during adolescence. Information on the bioenergetic state of normal children’s brain during development remains limited due to ethical concerns and overall complexity of conducting quantitative cerebral metabolic studies using positron emission tomography (PET) or magnetic resonance spectroscopy (MRS) Filling this gap in knowledge may shed light on several clinical predicaments and disease states including understanding the high incidence of benign febrile seizures in children 18 month of age (Pavlidou et al, 2013), the increased risk of longterm cognitive sequelae from multiple anesthesia and surgeries exposures before age 4 years (Glatz et al, 2017), and the higher rate of brain overgrowth observed in children with autism spectrum disorder (Hazlett et al, 2005; Sacco et al, 2015). The growth pattern of brain development is paralleled by age-varying energy requirements
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