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Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized ¹³C magnetic resonance.

ABSTRACT: The mammalian brain relies primarily on glucose as a fuel to meet its high metabolic demand. Among the various techniques used to study cerebral metabolism, ¹³C magnetic resonance spectroscopy (MRS) allows following the fate of ¹³C-enriched substrates through metabolic pathways. We herein demonstrate that it is possible to measure cerebral glucose metabolism in vivo with sub-second time resolution using hyperpolarized ¹³C MRS. In particular, the dynamic ¹³C-labeling of pyruvate and lactate formed from ¹³C-glucose was observed in real time. An ad-hoc synthesis to produce [2,3,4,6,6-²H₅, 3,4-¹³C₂]-D-glucose was developed to improve the ¹³C signal-to-noise ratio as compared to experiments performed following [U-²H₇, U-¹³C]-D-glucose injections. The main advantage of only labeling C3 and C4 positions is the absence of ¹³C-¹³C coupling in all downstream metabolic products after glucose is split into 3-carbon intermediates by aldolase. This unique method allows direct detection of glycolysis in vivo in the healthy brain in a noninvasive manner.

SUBMITTER: Mishkovsky M

PROVIDER: S-EPMC5601924 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized 13C magnetic resonance.

Mishkovsky Mor M Anderson Brian B Karlsson Magnus M Lerche Mathilde H MH Sherry A Dean AD Gruetter Rolf R Kovacs Zoltan Z Comment Arnaud A

Scientific reports 20170915 1

The mammalian brain relies primarily on glucose as a fuel to meet its high metabolic demand. Among the various techniques used to study cerebral metabolism, 13C magnetic resonance spectroscopy (MRS) allows following the fate of 13C-enriched substrates through metabolic pathways. We herein demonstrate that it is possible to measure cerebral glucose metabolism in vivo with sub-second time resolution using hyperpolarized 13C MRS. In particular, the dynamic 13</ ...[more]

PMID: 28916775

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Project description:Lipopolysaccharide (LPS) is a commonly used agent for induction of neuroinflammation in preclinical studies. Upon injection, LPS causes activation of microglia and astrocytes, whose metabolism alters to favor glycolysis. Assessing in vivo neuroinflammation and its modulation following therapy remains challenging, and new noninvasive methods allowing for longitudinal monitoring would be highly valuable. Hyperpolarized (HP) 13 C magnetic resonance spectroscopy (MRS) is a promising technique for assessing in vivo metabolism. In addition to applications in oncology, the most commonly used probe of [1-13 C] pyruvate has shown potential in assessing neuroinflammation-linked metabolism in mouse models of multiple sclerosis and traumatic brain injury. Here, we aimed to investigate LPS-induced neuroinflammatory changes using HP [1-13 C] pyruvate and HP 13 C urea. 2D chemical shift imaging following simultaneous intravenous injection of HP [1-13 C] pyruvate and HP 13 C urea was performed at baseline (day 0) and at days 3 and 7 post-intracranial injection of LPS (n = 6) or saline (n = 5). Immunofluorescence (IF) analyses were performed for Iba1 (resting and activated microglia/macrophages), GFAP (resting and reactive astrocytes) and CD68 (activated microglia/macrophages). A significant increase in HP [1-13 C] lactate production was observed at days 3 and 7 following injection, in the injected (ipsilateral) side of the LPS-treated mouse brain, but not in either the contralateral side or saline-injected animals. HP 13 C lactate/pyruvate ratio, without and with normalization to urea, was also significantly increased in the ipsilateral LPS-injected brain at 7 days compared with baseline. IF analyses showed a significant increase in CD68 and GFAP staining at 3 days, followed by increased numbers of Iba1 and GFAP positive cells at 7 days post-LPS injection. In conclusion, we can detect LPS-induced changes in the mouse brain using HP 13 C MRS, in alignment with increased numbers of microglia/macrophages and astrocytes. This study demonstrates that HP 13 C spectroscopy has substantial potential for providing noninvasive information on neuroinflammation.

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Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized ¹³C magnetic resonance.

Publications

Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized <sup>13</sup>C magnetic resonance.

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Dataset Information

Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized 13C magnetic resonance.

Publications

Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized &lt;sup&gt;13&lt;/sup&gt;C magnetic resonance.

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OmicsDI is part of the ELIXIR infrastructure

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Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized ¹³C magnetic resonance.

Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized <sup>13</sup>C magnetic resonance.