title: Neuroprotective role of lactate after cerebral ischemia.
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.
authors.affiliation: Department of Neurology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Carole
authors.initials: C
authors.lastname: Berthet
authors.forename: Hongxia
authors.initials: H
authors.lastname: Lei
authors.forename: Jonathan
authors.initials: J
authors.lastname: Thevenet
authors.forename: Rolf
authors.initials: R
authors.lastname: Gruetter
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Magistretti
authors.forename: Lorenz
authors.initials: L
authors.lastname: Hirt
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D019344:Lactic Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D018696:Neuroprotective Agents; D019344:Lactic Acid