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

Autor: Takado, Yuhei, Cheng, Tian, A M Bastiaansen, Jessica, A I Yoshihara, Hikari, Lanz, Bernard, Mishkovsky, Mor, Lengacher, Sylvain, Comment, Arnaud
Jazyk: angličtina
Rok vydání: 2018
Zdroj: ACS chemical neuroscience. 9(11):2554-2562
ISSN: 1948-7193
Popis: 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 magnetic resonance spectroscopy (MRS). Following the intravenous injection of hyperpolarized [1-C]lactate, we observed that the distribution of the 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-C]lactate to [1-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 C MRS can be used to detect a variation in cerebral lactate uptake of
Databáze: OpenAIRE