Hyperpolarized 13 C Magnetic Resonance Spectroscopy Reveals the Rate-Limiting Role of the Blood-Brain Barrier in the Cerebral Uptake and Metabolism of l-Lactate in Vivo

ACS Chemical Neuroscience
Yuhei TakadoArnaud Comment

Abstract

The dynamics of l-lactate transport across the blood-brain barrier (BBB) and its cerebral metabolism are still subject to debate. We studied lactate uptake and intracellular metabolism in the mouse brain using hyperpolarized 13C magnetic resonance spectroscopy (MRS). Following the intravenous injection of hyperpolarized [1-13C]lactate, we observed that the distribution of the 13C label between lactate and pyruvate, which has been shown to be representative of their pool size ratio, is different in NMRI and C57BL/6 mice, the latter exhibiting a higher level of cerebral lactate dehydrogenase A ( Ldha) expression. On the basis of this observation, and an additional set of experiments showing that the cerebral conversion of [1-13C]lactate to [1-13C]pyruvate increases after exposing the brain to ultrasound irradiation that reversibly opens the BBB, we concluded that lactate transport is rate-limited by the BBB, with a 30% increase in lactate uptake after its disruption. It was also deduced from these results that hyperpolarized 13C MRS can be used to detect a variation in cerebral lactate uptake of <40 nmol in a healthy brain during an in vivo experiment lasting only 75 s, opening new opportunities to study the role of lactate in br...Continue Reading

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Citations

Mar 11, 2020·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·James T GristFerdia A Gallagher
Sep 17, 2020·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Jun ChenJae Mo Park
Aug 26, 2020·Proceedings of the National Academy of Sciences of the United States of America·Yi RaoDavid Piwnica-Worms
Mar 7, 2020·Fluids and Barriers of the CNS·Richard F KeepLester R Drewes
Jun 6, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Nicholas R PerkonsTerence P F Gade
May 9, 2021·NMR in Biomedicine·Angus Z LauCharles H Cunningham
Mar 16, 2019·ACS Chemical Neuroscience·Tom H PeetersTom W J Scheenen

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