Neuroprotective role of lactate after cerebral ischemia.

Details

Serval ID
serval:BIB_35DC3E05F74D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Neuroprotective role of lactate after cerebral ischemia.
Journal
Journal of Cerebral Blood Flow and Metabolism
Author(s)
Berthet C., Lei H., Thevenet J., Gruetter R., Magistretti P.J., Hirt L.
ISSN
1559-7016[electronic], 0271-678X[linking]
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
29
Number
11
Pages
1780-1789
Language
english
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
Animals, Brain Ischemia/pathology, Brain Ischemia/physiopathology, Brain Lactate, Cell Death/drug effects, Disease Models, Animal, Dose-Response Relationship, Drug, Energy Substrate, Hippocampus/drug effects, Hippocampus/pathology, Inbred Strains, Injections, Intraventricular, In-Vitro, Lactic Acid/administration & dosage, Lactic Acid/pharmacology, L-Lactate, Magnetic Resonance Spectroscopy, Magnetic-Resonance-Spectroscopy, Male, Mice, Mice, Inbred ICR, Middle Cerebral Artery Occlusion, Mouse-Brain, Neurochemical Profile, Neuroprotective Agents/administration & dosage, Neuroprotective Agents/pharmacology, Oxygen And Glucose Deprivation, Periinfarct Depolarizations, Rat, Rats, Synaptic Function, Vivo H-1-Nmr Spectroscopy
Pubmed
Web of science
Create date
25/02/2010 16:33
Last modification date
20/08/2019 13:23
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