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

Frontiers in Physiology
Lara BuscemiLorenz Hirt

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 t...Continue Reading

References

Jan 1, 1989·Stroke; a Journal of Cerebral Circulation·E Z LongaR Cummins
Oct 25, 1994·Proceedings of the National Academy of Sciences of the United States of America·L Pellerin, P J Magistretti
Jun 5, 2004·Stroke; a Journal of Cerebral Circulation·Lorenz HirtJulien Bogousslavsky
Jul 30, 2004·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Alastair B RossAfaf Kamal-Eldin
Dec 7, 2007·British Journal of Pharmacology·E KellyG Henderson
Oct 28, 2008·Biochemical and Biophysical Research Communications·Tian-Quan CaiM Gerard Waters
Dec 3, 2008·The Journal of Biological Chemistry·Changlu LiuTimothy W Lovenberg
Feb 19, 2009·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Hongxia LeiRolf Gruetter
Aug 14, 2009·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Carole BerthetLorenz Hirt
Oct 20, 2009·Trends in Pharmacological Sciences·Kashan AhmedStefan Offermanns
Oct 12, 2010·Neurochemistry International·Tobias Horn, Jochen Klein
Mar 8, 2011·Cell·Akinobu SuzukiCristina M Alberini
Mar 22, 2012·The Journal of Pharmacology and Experimental Therapeutics·Changlu LiuTimothy W Lovenberg
Mar 30, 2012·Frontiers in Neuroenergetics·Linda H Bergersen, Albert Gjedde
May 23, 2012·Neurochemical Research·Mauro DinuzzoFederico Giove
Jan 10, 2013·Neurochemistry International·Tobias Horn, Jochen Klein
Jul 26, 2013·Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research·Sherrefa R BurchellJohn H Zhang
Jan 31, 2014·Intensive Care Medicine·Pierre BouzatMauro Oddo
Feb 13, 2014·Nature Communications·F TangA G Teschemacher
Aug 9, 2012·ACS Medicinal Chemistry Letters·Curt A DvorakNicholas I Carruthers
Jun 15, 2014·Mitochondrion·M Adeva-AndanyJ Rodríguez-Seijas
Jul 30, 2014·Proceedings of the National Academy of Sciences of the United States of America·Jiangyan YangPierre J Magistretti
Jun 4, 2015·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Ximena CastilloLorenz Hirt
Dec 25, 2015·Cell Metabolism·Philipp MächlerBruno Weber
Feb 1, 2017·Cellular Signalling·Sudarshan Rajagopal, Sudha K Shenoy
Oct 6, 2017·JCI Insight·Kristina WalleniusNicholas D Oakes
Mar 9, 2018·Nature Reviews. Neuroscience·Pierre J Magistretti, Igor Allaman
Apr 29, 2018·Hippocampus·Gabriel Herrera-López, Emilio J Galván
Jun 6, 2018·Frontiers in Molecular Neuroscience·Nina VardjanRobert Zorec
Jul 8, 2018·Experimental & Molecular Medicine·Jing ZhouYang Wang
Oct 26, 2018·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Camille BlochetLorenz Hirt
Feb 8, 2019·Frontiers in Neuroscience·Carlos-Alberto GonçalvesMarina C Leite
Mar 19, 2019·Investigative Ophthalmology & Visual Science·Rupali VohraMiriam Kolko
Mar 31, 2019·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Haíssa de Castro AbrantesJean-Yves Chatton
Jun 11, 2019·Frontiers in Neuroscience·Yaeli Lev-VachnishEitan Okun

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