Format

Send to

Choose Destination
ACS Chem Neurosci. 2018 Nov 21;9(11):2554-2562. doi: 10.1021/acschemneuro.8b00066. Epub 2018 May 25.

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

Author information

1
Institute of Physics of Biological Systems , Ecole Polytechnique Fédérale de Lausanne , CH-1015 Lausanne , Switzerland.
2
Department of Functional Brain Imaging Research , National Institutes for Quantum and Radiological Science and Technology , Chiba , Japan.
3
Cancer Research UK Cambridge Institute , University of Cambridge , Li Ka Shing Centre , Cambridge , United Kingdom.
4
Laboratory of Functional and Metabolic Imaging , Ecole Polytechnique Fédérale de Lausanne , CH-1015 Lausanne , Switzerland.
5
Department of Radiology , University Hospital Lausanne (CHUV) and University of Lausanne (UNIL) , Lausanne , Switzerland.
6
Sir Peter Mansfield Magnetic Resonance Center , The University of Nottingham , Nottingham NG7 2RD , United Kingdom.
7
Laboratory of Neuroenergetics and Cellular Dynamics , Ecole Polytechnique Fédérale de Lausanne , CH-1015 Lausanne , Switzerland.
8
General Electric Healthcare , Chalfont St Giles , Buckinghamshire HP8 4SP , United Kingdom.

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 brain metabolism.

KEYWORDS:

Hyperpolarization; bicarbonate; dynamic nuclear polarization; magnetic resonance spectroscopy; pyruvate; ultrasound

Supplemental Content

Full text links

Icon for American Chemical Society Icon for PubMed Central
Loading ...
Support Center