ROUMES, Helene; DUMONT, Ursule; SANCHEZ, Stephane; MAZUEL, Leslie; BLANC, Jordy; RAFFARD, Gerard; CHATEIL, Jean-Francois; PELLERIN, Luc; BOUZIER-SORE, Anne-Karine

doi:10.1177/0271678x20908355

ROUMES, Helene
Centre de résonance magnétique des systèmes biologiques [CRMSB]

DUMONT, Ursule

Centre de résonance magnétique des systèmes biologiques [CRMSB]

SANCHEZ, Stephane
Centre de résonance magnétique des systèmes biologiques [CRMSB]

Langue

Article de revue

Ce document a été publié dans

Journal of Cerebral Blood Flow and Metabolism. 2020-03-24, vol. 41, n° 2, p. 342-358

Résumé en anglais

Hypoxic-ischemic (HI) encephalopathy remains a major cause of perinatal mortality and chronic disability in newborns worldwide (1–6 for 1000 births). The only current clinical treatment is hypothermia, which is efficient for less than 60% of babies. Mainly considered as a waste product in the past, lactate, in addition to glucose, is increasingly admitted as a supplementary fuel for neurons and, more recently, as a signaling molecule in the brain. Our aim was to investigate the neuroprotective effect of lactate in a neonatal (seven day old) rat model of hypoxia-ischemia. Pups received intra-peritoneal injection(s) of lactate (40 μmol). Size and apparent diffusion coefficients of brain lesions were assessed by magnetic resonance diffusion-weighted imaging. Oxiblot analyses and long-term behavioral studies were also conducted. A single lactate injection induced a 30% reduction in brain lesion volume, indicating a rapid and efficient neuroprotective effect. When oxamate, a lactate dehydrogenase inhibitor, was co-injected with lactate, the neuroprotection was completely abolished, highlighting the role of lactate metabolism in this protection. After three lactate injections (one per day), pups presented the smallest brain lesion volume and a complete recovery of neurological reflexes, sensorimotor capacities and long-term memory, demonstrating that lactate administration is a promising therapy for neonatal HI insult.< Réduire

Mots clés en anglais

Neonatal hypoxia-ischemia

Lactate

Neuroprotection

Astrocyte to neuron lactate shuttle

MRI

URI

https://oskar-bordeaux.fr/handle/20.500.12278/148383

DOI

http://dx.doi.org/10.1177/0271678x20908355

Project ANR

Translational Research and Advanced Imaging Laboratory
Initiative d'excellence de l'Université de Bordeaux
Exploration in vivo du couplage métabolique entre neurones et astrocytes lors de l'activation cérébrale: étude par spectroscopie de RMN - ANR-15-CE37-0012

Unités de recherche

Centre de Résonance Magnétique des Systèmes Biologiques (CRMSB) - UMR 5536

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Neuroprotective role of lactate in rat neonatal hypoxia-ischemia