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  4. Hyperpolarized C-13 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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research article

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

Takado, Yuhei  
•
Cheng, Tian  
•
Bastiaansen, Jessica A. M.  
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November 1, 2018
Acs Chemical Neuroscience

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 C-13 magnetic resonance spectroscopy (MRS). Following the intravenous injection of hyperpolarized [1-C-13]lactate, we observed that the distribution of the C-13 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-C-13]lactate to [1-C-13]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 C-13 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.

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Type
research article
DOI
10.1021/acschemneuro.8b00066
Web of Science ID

WOS:000451496200007

Author(s)
Takado, Yuhei  
•
Cheng, Tian  
•
Bastiaansen, Jessica A. M.  
•
Yoshihara, Hikari A. I.  
•
Lanz, Bernard  
•
Mishkovsky, Mor  
•
Lengacher, Sylvain  
•
Comment, Arnaud  
Date Issued

2018-11-01

Published in
Acs Chemical Neuroscience
Volume

9

Issue

11

Start page

2554

End page

2562

Subjects

Biochemistry & Molecular Biology

•

Chemistry, Medicinal

•

Neurosciences

•

Pharmacology & Pharmacy

•

Neurosciences & Neurology

•

hyperpolarization

•

magnetic resonance spectroscopy

•

dynamic nuclear polarization

•

ultrasound

•

pyruvate

•

bicarbonate

•

inhibition

•

mrs

•

substrate

•

infusion

•

exchange

•

ldh

•

CIBM-AIT

Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LIFMET  
CIBM  
LNDC  
Available on Infoscience
December 13, 2018
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/152136
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