Hyperpolarized <sup>13</sup>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.

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Serval ID
serval:BIB_8A3E59B47AC1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Hyperpolarized <sup>13</sup>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.
Journal
ACS chemical neuroscience
Author(s)
Takado Y., Cheng T., Bastiaansen JAM, Yoshihara HAI, Lanz B., Mishkovsky M., Lengacher S., Comment A.
ISSN
1948-7193 (Electronic)
ISSN-L
1948-7193
Publication state
Published
Issued date
21/11/2018
Peer-reviewed
Oui
Volume
9
Number
11
Pages
2554-2562
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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 <sup>13</sup> C magnetic resonance spectroscopy (MRS). Following the intravenous injection of hyperpolarized [1- <sup>13</sup> C]lactate, we observed that the distribution of the <sup>13</sup> C 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- <sup>13</sup> C]lactate to [1- <sup>13</sup> C]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 <sup>13</sup> C 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 brain metabolism.
Keywords
Animals, Blood-Brain Barrier/metabolism, Blood-Brain Barrier/radiation effects, Brain/metabolism, Brain/radiation effects, Carbon-13 Magnetic Resonance Spectroscopy, L-Lactate Dehydrogenase/genetics, L-Lactate Dehydrogenase/metabolism, Lactic Acid/metabolism, Lactic Acid/radiation effects, Male, Mice, Mice, Inbred C57BL, Pyruvic Acid/metabolism, Pyruvic Acid/radiation effects, Ultrasonic Waves, Hyperpolarization, bicarbonate, dynamic nuclear polarization, magnetic resonance spectroscopy, pyruvate, ultrasound
Pubmed
Web of science
Open Access
Yes
Create date
03/07/2018 10:56
Last modification date
04/01/2020 6:17
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