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
Version 3 2019-05-17, 08:13
Version 2 2018-06-22, 17:26
Version 1 2018-05-25, 12:33
Posted on 2019-05-17 - 08:13
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.
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Takado, Yuhei; Cheng, Tian; Bastiaansen, Jessica A. M.; Yoshihara, Hikari A. I.; Lanz, Bernard; Mishkovsky, Mor; et al. (2018). 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. ACS Publications. Collection. https://doi.org/10.1021/acschemneuro.8b00066
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AUTHORS (8)
YT
Yuhei Takado
TC
Tian Cheng
JB
Jessica A. M. Bastiaansen
HY
Hikari A. I. Yoshihara
BL
Bernard Lanz
MM
Mor Mishkovsky
SL
Sylvain Lengacher
AC
Arnaud Comment