Evaluating the Potential of Hyperpolarised [1-C] L-lactate As a Neuroprotectant Metabolic Biosensor for Stroke

Overview

Journal Sci Rep

Specialty Science

Date 2020 Mar 29

PMID 32218474

Citations 16

Authors

Jean-Noel Hyacinthe

Lara Buscemi

Thanh Phong Le

Mario Lepore

Lorenz Hirt

Mor Mishkovsky

Affiliations

Soon will be listed here.

Abstract

Cerebral metabolism, which can be monitored by magnetic resonance spectroscopy (MRS), changes rapidly after brain ischaemic injury. Hyperpolarisation techniques boost C MRS sensitivity by several orders of magnitude, thereby enabling in vivo monitoring of biochemical transformations of hyperpolarised (HP) C-labelled precursors with a time resolution of seconds. The exogenous administration of the metabolite L-lactate was shown to decrease lesion size and ameliorate neurological outcome in preclinical studies in rodent stroke models, as well as influencing brain metabolism in clinical pilot studies of acute brain injury patients. The aim of this study was to demonstrate the feasibility of measuring HP [1-C] L-lactate metabolism in real-time in the mouse brain after ischaemic stroke when administered after reperfusion at a therapeutic dose. We showed a rapid, time-after-reperfusion-dependent conversion of [1-C] L-lactate to [1-C] pyruvate and [C] bicarbonate that brings new insights into the neuroprotection mechanism of L-lactate. Moreover, this study paves the way for the use of HP [1-C] L-lactate as a sensitive molecular-imaging biosensor in ischaemic stroke patients after endovascular clot removal.

Citing Articles

Cerebral net uptake of lactate contributes to neurological injury after experimental cardiac arrest in rabbits.

Estelle F, Faucher E, Alexandra D, Demelos A, Emilie B, Boissady E Sci Rep. 2024; 14(1):24600.

PMID: 39426990 PMC: 11490571. DOI: 10.1038/s41598-024-74660-6.

Influence of DNP Polarizing Agents on Biochemical Processes: TEMPOL in Transient Ischemic Stroke.

Le T, Buscemi L, Lepore M, Mishkovsky M, Hyacinthe J, Hirt L ACS Chem Neurosci. 2023; 14(17):3013-3018.

PMID: 37603041 PMC: 10485885. DOI: 10.1021/acschemneuro.3c00137.

Multi-sample/multi-nucleus parallel polarization and monitoring enabled by a fluid path technology compatible cryogenic probe for dissolution dynamic nuclear polarization.

Le T, Hyacinthe J, Capozzi A Sci Rep. 2023; 13(1):7962.

PMID: 37198242 PMC: 10192315. DOI: 10.1038/s41598-023-34958-3.

Functional noninvasive detection of glycolytic pancreatic ductal adenocarcinoma.

Heid I, Munch C, Karakaya S, Lueong S, Winkelkotte A, Liffers S Cancer Metab. 2022; 10(1):24.

PMID: 36494842 PMC: 9737747. DOI: 10.1186/s40170-022-00298-5.

Lactate Neuroprotection against Transient Ischemic Brain Injury in Mice Appears Independent of HCAR1 Activation.

Buscemi L, Price M, Castillo-Gonzalez J, Chatton J, Hirt L Metabolites. 2022; 12(5).

PMID: 35629969 PMC: 9145226. DOI: 10.3390/metabo12050465.

References

Schwamberger K, Bodner E . [Primary idiopathetic torsion of the omentum]. Zentralbl Chir. 1972; 97(12):369-71. View

Thomalla G, Gerloff C . Acute imaging for evidence-based treatment of ischemic stroke. Curr Opin Neurol. 2019; 32(4):521-529. DOI: 10.1097/WCO.0000000000000716. View

Ros J, Pecinska N, Alessandri B, Landolt H, Fillenz M . Lactate reduces glutamate-induced neurotoxicity in rat cortex. J Neurosci Res. 2001; 66(5):790-4. DOI: 10.1002/jnr.10043. View

Berthet C, Castillo X, Magistretti P, Hirt L . New evidence of neuroprotection by lactate after transient focal cerebral ischaemia: extended benefit after intracerebroventricular injection and efficacy of intravenous administration. Cerebrovasc Dis. 2012; 34(5-6):329-35. DOI: 10.1159/000343657. View

Ichai C, Armando G, Orban J, Berthier F, Rami L, Samat-Long C . Sodium lactate versus mannitol in the treatment of intracranial hypertensive episodes in severe traumatic brain-injured patients. Intensive Care Med. 2008; 35(3):471-9. DOI: 10.1007/s00134-008-1283-5. View

Carteron L, Solari D, Patet C, Quintard H, Miroz J, Bloch J . Hypertonic Lactate to Improve Cerebral Perfusion and Glucose Availability After Acute Brain Injury. Crit Care Med. 2018; 46(10):1649-1655. DOI: 10.1097/CCM.0000000000003274. View

Figlewski K, Andersen H, Staermose T, von Weitzel-Mudersbach P, Nielsen J, Blicher J . Decreased GABA levels in the symptomatic hemisphere in patients with transient ischemic attack. Heliyon. 2018; 4(9):e00790. PMC: 6154475. DOI: 10.1016/j.heliyon.2018.e00790. View

Mishkovsky M, Comment A . Hyperpolarized MRS: New tool to study real-time brain function and metabolism. Anal Biochem. 2016; 529:270-277. DOI: 10.1016/j.ab.2016.09.020. View

Mishkovsky M, Anderson B, Karlsson M, Lerche M, Sherry A, Gruetter R . Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized C magnetic resonance. Sci Rep. 2017; 7(1):11719. PMC: 5601924. DOI: 10.1038/s41598-017-12086-z. View

10.

Guglielmetti C, Chou A, Krukowski K, Najac C, Feng X, Riparip L . In vivo metabolic imaging of Traumatic Brain Injury. Sci Rep. 2017; 7(1):17525. PMC: 5727520. DOI: 10.1038/s41598-017-17758-4. View

12.

Marjanska M, Shestov A, Deelchand D, Kittelson E, Henry P . Brain metabolism under different anesthetic conditions using hyperpolarized [1- C]pyruvate and [2- C]pyruvate. NMR Biomed. 2018; 31(12):e4012. PMC: 6449100. DOI: 10.1002/nbm.4012. View

13.

Miloushev V, Granlund K, Boltyanskiy R, Lyashchenko S, DeAngelis L, Mellinghoff I . Metabolic Imaging of the Human Brain with Hyperpolarized C Pyruvate Demonstrates C Lactate Production in Brain Tumor Patients. Cancer Res. 2018; 78(14):3755-3760. PMC: 6050093. DOI: 10.1158/0008-5472.CAN-18-0221. View

14.

Nery F, De Vita E, Clark C, Gordon I, Thomas D . Robust kidney perfusion mapping in pediatric chronic kidney disease using single-shot 3D-GRASE ASL with optimized retrospective motion correction. Magn Reson Med. 2018; 81(5):2972-2984. DOI: 10.1002/mrm.27614. View

15.

Sternberg D . Biologic tests in psychiatry. Psychiatr Clin North Am. 1984; 7(3):639-50. View

16.

ALEXANDER R . Contractile mechanics of venous smooth muscle. Am J Physiol. 1967; 212(4):852-8. DOI: 10.1152/ajplegacy.1967.212.4.852. View

18.

BATES C . Racially determined abnormal essential fatty acid and prostaglandin metabolism and food allergies linked to autoimmune, inflammatory, and psychiatric disorders among Coastal British Columbia Indians. Med Hypotheses. 1988; 25(2):103-9. DOI: 10.1016/0306-9877(88)90026-6. View

19.

Cheng T, Mishkovsky M, Bastiaansen J, Ouari O, Hautle P, Tordo P . Automated transfer and injection of hyperpolarized molecules with polarization measurement prior to in vivo NMR. NMR Biomed. 2013; 26(11):1582-8. DOI: 10.1002/nbm.2993. View

20.

Mlynarik V, Gambarota G, Frenkel H, Gruetter R . Localized short-echo-time proton MR spectroscopy with full signal-intensity acquisition. Magn Reson Med. 2006; 56(5):965-70. DOI: 10.1002/mrm.21043. View

21.

Pierre K, Pellerin L, Debernardi R, Riederer B, Magistretti P . Cell-specific localization of monocarboxylate transporters, MCT1 and MCT2, in the adult mouse brain revealed by double immunohistochemical labeling and confocal microscopy. Neuroscience. 2000; 100(3):617-27. DOI: 10.1016/s0306-4522(00)00294-3. View

22.

Rosafio K, Castillo X, Hirt L, Pellerin L . Cell-specific modulation of monocarboxylate transporter expression contributes to the metabolic reprograming taking place following cerebral ischemia. Neuroscience. 2016; 317:108-20. DOI: 10.1016/j.neuroscience.2015.12.052. View