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Neuroprotective role of lactate after cerebral ischemia

Berthet, Carole
Thevenet, Jonathan
Hirt, Lorenz
Published in Journal of cerebral blood flow and metabolism. 2009, vol. 29, no. 11, p. 1780-9
Abstract It is well established that lactate can be used as an energy substrate by the brain by conversion to pyruvate and a subsequent oxidation in the mitochondria. Knowing the need for readily metabolizable substrates directly after ischemia and the protective effect of lactate after excitotoxicity, the aim of this study was to investigate whether lactate administration directly after ischemia could be neuroprotective. In vitro, the addition of 4 mmol/L L-lactate to the medium of rat organotypic hippocampal slices, directly after oxygen and glucose deprivation (OGD), protected against neuronal death, whereas a higher dose of 20 mmol/L was toxic. In vivo, after middle cerebral artery occlusion in the mouse, an intracerebroventricular injection of 2 microL of 100 mmol/L L-lactate, immediately after reperfusion, led to a significant decrease in lesion size, which was more pronounced in the striatum, and an improvement in neurologic outcome. A later injection 1 h after reperfusion did not reduce lesion size, but significantly improved neurologic outcome, which is an important point in the context of a potential clinical application. Therefore, a moderate increase in lactate after ischemia may be a therapeutic tool.
Keywords AnimalsBrain Ischemia/pathology/physiopathology/prevention & controlCell Death/drug effectsDisease Models, AnimalDose-Response Relationship, DrugHippocampus/drug effects/pathologyInjections, IntraventricularLactic Acid/administration & dosage/pharmacology/therapeutic useMaleMiceMice, Inbred ICRNeuroprotective Agents/administration & dosage/pharmacology/therapeutic useRatsRats, Inbred Strains
PMID: 19675565
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BERTHET, Carole et al. Neuroprotective role of lactate after cerebral ischemia. In: Journal of cerebral blood flow and metabolism, 2009, vol. 29, n° 11, p. 1780-9. doi: 10.1038/jcbfm.2009.97 https://archive-ouverte.unige.ch/unige:32990

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Deposited on : 2014-01-09

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