Evaluating the potential of hyperpolarised [1-13C] L-lactate as a neuroprotectant metabolic biosensor for stroke

Hyacinthe, Jean-Noël (Geneva School of Health Sciences, HES-SO University of Applied Sciences and Arts Western Switzerland ; University of Geneva, Geneva, Switzerland) ; Buscemi, Lara (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland) ; Lê, Thanh Phong (Geneva School of Health Sciences, HES-SO University of Applied Sciences and Arts Western Switzerland ; École polytechnique fédérale de Lausanne (EPFL), Lausanne, Switzerland) ; Lepore, Mario (École polytechnique fédérale de Lausanne (EPFL), Lausanne, Switzerland) ; Hirt, Lorenz (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland) ; Mishkovsky, Mor (École polytechnique fédérale de Lausanne (EPFL), Lausanne, Switzerland)

Cerebral metabolism, which can be monitored by magnetic resonance spectroscopy (MRS), changes rapidly after brain ischaemic injury. Hyperpolarisation techniques boost 13C MRS sensitivity by several orders of magnitude, thereby enabling in vivo monitoring of biochemical transformations of hyperpolarised (HP) 13C-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 [1-13C] 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 [1-13C] L-lactate to [1-13C] pyruvate and [13C] bicarbonate that brings new insights into the neuroprotection mechanism of L-lactate. Moreover, this study paves the way for the use of HP [1-13C] L-lactate as a sensitive molecular-imaging biosensor in ischaemic stroke patients after endovascular clot removal.


Keywords:
Article Type:
scientifique
Faculty:
Santé
School:
HEdS - Genève
Institute:
Aucun institut
Date:
2020-03
Pagination:
11 p.
Published in:
Scientific Reports
Numeration (vol. no.):
2020, vol. 10, article 5507
DOI:
ISSN:
2045-2322
Appears in Collection:



 Record created 2020-04-16, last modified 2020-06-04

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