Hydroxycarboxylic Acid Receptor 1 and Neuroprotection in a Mouse Model of Cerebral Ischemia-Reperfusion.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_96EF19E2924E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Hydroxycarboxylic Acid Receptor 1 and Neuroprotection in a Mouse Model of Cerebral Ischemia-Reperfusion.
Journal
Frontiers in physiology
Author(s)
Buscemi L., Blochet C., Magistretti P.J., Hirt L.
ISSN
1664-042X (Print)
ISSN-L
1664-042X
Publication state
Published
Issued date
2021
Peer-reviewed
Oui
Volume
12
Pages
689239
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Lactate is an intriguing molecule with emerging physiological roles in the brain. It has beneficial effects in animal models of acute brain injuries and traumatic brain injury or subarachnoid hemorrhage patients. However, the mechanism by which lactate provides protection is unclear. While there is evidence of a metabolic effect of lactate providing energy to deprived neurons, it can also activate the hydroxycarboxylic acid receptor 1 (HCAR1), a Gi-coupled protein receptor that modulates neuronal firing rates. After cerebral hypoxia-ischemia, endogenously produced brain lactate is largely increased, and the exogenous administration of more lactate can decrease lesion size and ameliorate the neurological outcome. To test whether HCAR1 plays a role in lactate-induced neuroprotection, we injected the agonists 3-chloro-5-hydroxybenzoic acid and 3,5-dihydroxybenzoic acid into mice subjected to 30-min middle cerebral artery occlusion. The in vivo administration of HCAR1 agonists at reperfusion did not appear to exert any relevant protective effect as seen with lactate administration. Our results suggest that the protective effects of lactate after hypoxia-ischemia come rather from the metabolic effects of lactate than its signaling through HCAR1.
Keywords
Physiology (medical), Physiology, hydroxycarboxylic acid receptor 1, ischemia, lactate, metabolism, middle cerebral artery occlusion, neuroprotection
Pubmed
Web of science
Open Access
Yes
Create date
11/06/2021 9:32
Last modification date
12/01/2022 7:12
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