A probable dual mode of action for both L- and D-lactate neuroprotection in cerebral ischemia.

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Version: Author's accepted manuscript
Serval ID
serval:BIB_A6C4D01230E8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A probable dual mode of action for both L- and D-lactate neuroprotection in cerebral ischemia.
Journal
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
Author(s)
Castillo X., Rosafio K., Wyss M.T., Drandarov K., Buck A., Pellerin L., Weber B., Hirt L.
ISSN
1559-7016 (Electronic)
ISSN-L
0271-678X
Publication state
Published
Issued date
10/2015
Peer-reviewed
Oui
Volume
35
Number
10
Pages
1561-1569
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Lactate has been shown to offer neuroprotection in several pathologic conditions. This beneficial effect has been attributed to its use as an alternative energy substrate. However, recent description of the expression of the HCA1 receptor for lactate in the central nervous system calls for reassessment of the mechanism by which lactate exerts its neuroprotective effects. Here, we show that HCA1 receptor expression is enhanced 24 hours after reperfusion in an middle cerebral artery occlusion stroke model, in the ischemic cortex. Interestingly, intravenous injection of L-lactate at reperfusion led to further enhancement of HCA1 receptor expression in the cortex and striatum. Using an in vitro oxygen-glucose deprivation model, we show that the HCA1 receptor agonist 3,5-dihydroxybenzoic acid reduces cell death. We also observed that D-lactate, a reputedly non-metabolizable substrate but partial HCA1 receptor agonist, also provided neuroprotection in both in vitro and in vivo ischemia models. Quite unexpectedly, we show D-lactate to be partly extracted and oxidized by the rodent brain. Finally, pyruvate offered neuroprotection in vitro whereas acetate was ineffective. Our data suggest that L- and D-lactate offer neuroprotection in ischemia most likely by acting as both an HCA1 receptor agonist for non-astrocytic (most likely neuronal) cells as well as an energy substrate.

Keywords
Animals, Behavior, Animal/drug effects, Brain Chemistry/drug effects, Brain Ischemia/drug therapy, Brain Ischemia/pathology, Brain Ischemia/psychology, Carrier Proteins/biosynthesis, Carrier Proteins/genetics, Cell Death, Glucose/deficiency, Hippocampus/drug effects, Hypoxia, Brain/pathology, Immunohistochemistry, Kinetics, Lactic Acid/therapeutic use, Male, Mice, Nerve Tissue Proteins/biosynthesis, Nerve Tissue Proteins/genetics, Neuroprotective Agents/therapeutic use, Organ Culture Techniques, Signal Transduction/physiology, Stereoisomerism
Pubmed
Create date
18/01/2016 15:22
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20/08/2019 15:11
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