Lactate Neuroprotection against Transient Ischemic Brain Injury in Mice Appears Independent of HCAR1 Activation
Lactate can protect against damage caused by acute brain injuries both in rodents and in human patients. Besides its role as a metabolic support and alleged preferred neuronal fuel in stressful situations, an additional signaling mechanism mediated by the hydroxycarboxylic acid receptor 1 (HCAR1) wa...
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MDPI AG
2022-05-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/12/5/465 |
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| author | Lara Buscemi Melanie Price Julia Castillo-González Jean-Yves Chatton Lorenz Hirt |
| author_facet | Lara Buscemi Melanie Price Julia Castillo-González Jean-Yves Chatton Lorenz Hirt |
| author_sort | Lara Buscemi |
| collection | DOAJ |
| description | Lactate can protect against damage caused by acute brain injuries both in rodents and in human patients. Besides its role as a metabolic support and alleged preferred neuronal fuel in stressful situations, an additional signaling mechanism mediated by the hydroxycarboxylic acid receptor 1 (HCAR1) was proposed to account for lactate’s beneficial effects. However, the administration of HCAR1 agonists to mice subjected to middle cerebral artery occlusion (MCAO) at reperfusion did not appear to exert any relevant protective effect. To further evaluate the involvement of HCAR1 in the protection against ischemic damage, we looked at the effect of HCAR1 absence. We subjected wild-type and HCAR1 KO mice to transient MCAO followed by treatment with either vehicle or lactate. In the absence of HCAR1, the ischemic damage inflicted by MCAO was less pronounced, with smaller lesions and a better behavioral outcome than in wild-type mice. The lower susceptibility of HCAR1 KO mice to ischemic injury suggests that lactate-mediated protection is not achieved or enhanced by HCAR1 activation, but rather attributable to its metabolic effects or related to other signaling pathways. Additionally, in light of these results, we would disregard HCAR1 activation as an interesting therapeutic strategy for stroke patients. |
| first_indexed | 2024-03-10T03:25:44Z |
| format | Article |
| id | doaj.art-1837b382f62743a093f3ce23b6d4866d |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T03:25:44Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-1837b382f62743a093f3ce23b6d4866d2023-11-23T12:07:52ZengMDPI AGMetabolites2218-19892022-05-0112546510.3390/metabo12050465Lactate Neuroprotection against Transient Ischemic Brain Injury in Mice Appears Independent of HCAR1 ActivationLara Buscemi0Melanie Price1Julia Castillo-González2Jean-Yves Chatton3Lorenz Hirt4Stroke Laboratory, Neurology Service, Department of Clinical Neurosciences, Lausanne University Hospital Centre and University of Lausanne, CH-1011 Lausanne, SwitzerlandStroke Laboratory, Neurology Service, Department of Clinical Neurosciences, Lausanne University Hospital Centre and University of Lausanne, CH-1011 Lausanne, SwitzerlandStroke Laboratory, Neurology Service, Department of Clinical Neurosciences, Lausanne University Hospital Centre and University of Lausanne, CH-1011 Lausanne, SwitzerlandDepartment of Fundamental Neurosciences, University of Lausanne, CH-1005 Lausanne, SwitzerlandStroke Laboratory, Neurology Service, Department of Clinical Neurosciences, Lausanne University Hospital Centre and University of Lausanne, CH-1011 Lausanne, SwitzerlandLactate can protect against damage caused by acute brain injuries both in rodents and in human patients. Besides its role as a metabolic support and alleged preferred neuronal fuel in stressful situations, an additional signaling mechanism mediated by the hydroxycarboxylic acid receptor 1 (HCAR1) was proposed to account for lactate’s beneficial effects. However, the administration of HCAR1 agonists to mice subjected to middle cerebral artery occlusion (MCAO) at reperfusion did not appear to exert any relevant protective effect. To further evaluate the involvement of HCAR1 in the protection against ischemic damage, we looked at the effect of HCAR1 absence. We subjected wild-type and HCAR1 KO mice to transient MCAO followed by treatment with either vehicle or lactate. In the absence of HCAR1, the ischemic damage inflicted by MCAO was less pronounced, with smaller lesions and a better behavioral outcome than in wild-type mice. The lower susceptibility of HCAR1 KO mice to ischemic injury suggests that lactate-mediated protection is not achieved or enhanced by HCAR1 activation, but rather attributable to its metabolic effects or related to other signaling pathways. Additionally, in light of these results, we would disregard HCAR1 activation as an interesting therapeutic strategy for stroke patients.https://www.mdpi.com/2218-1989/12/5/465lactateneuroprotectionMCAOischemiastrokeHCAR1 |
| spellingShingle | Lara Buscemi Melanie Price Julia Castillo-González Jean-Yves Chatton Lorenz Hirt Lactate Neuroprotection against Transient Ischemic Brain Injury in Mice Appears Independent of HCAR1 Activation Metabolites lactate neuroprotection MCAO ischemia stroke HCAR1 |
| title | Lactate Neuroprotection against Transient Ischemic Brain Injury in Mice Appears Independent of HCAR1 Activation |
| title_full | Lactate Neuroprotection against Transient Ischemic Brain Injury in Mice Appears Independent of HCAR1 Activation |
| title_fullStr | Lactate Neuroprotection against Transient Ischemic Brain Injury in Mice Appears Independent of HCAR1 Activation |
| title_full_unstemmed | Lactate Neuroprotection against Transient Ischemic Brain Injury in Mice Appears Independent of HCAR1 Activation |
| title_short | Lactate Neuroprotection against Transient Ischemic Brain Injury in Mice Appears Independent of HCAR1 Activation |
| title_sort | lactate neuroprotection against transient ischemic brain injury in mice appears independent of hcar1 activation |
| topic | lactate neuroprotection MCAO ischemia stroke HCAR1 |
| url | https://www.mdpi.com/2218-1989/12/5/465 |
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