Extended preclinical investigation of lactate for neuroprotection after ischemic stroke
Lactate has been shown to have beneficial effect both in experimental ischemia–reperfusion models and in human acute brain injury patients. To further investigate lactate’s neuroprotective action in experimental in vivo ischemic stroke models prior to its use in clinics, we tested (1) the outcome of...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-02-01
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| Series: | Clinical and Translational Neuroscience |
| Online Access: | https://doi.org/10.1177/2514183X20904571 |
| _version_ | 1818367502001897472 |
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| author | Lara Buscemi Camille Blochet Melanie Price Pierre J Magistretti Hongxia Lei Lorenz Hirt |
| author_facet | Lara Buscemi Camille Blochet Melanie Price Pierre J Magistretti Hongxia Lei Lorenz Hirt |
| author_sort | Lara Buscemi |
| collection | DOAJ |
| description | Lactate has been shown to have beneficial effect both in experimental ischemia–reperfusion models and in human acute brain injury patients. To further investigate lactate’s neuroprotective action in experimental in vivo ischemic stroke models prior to its use in clinics, we tested (1) the outcome of lactate administration on permanent ischemia and (2) its compatibility with the only currently approved drug for the treatment of acute ischemic stroke, recombinant tissue plasminogen activator (rtPA), after ischemia–reperfusion. We intravenously injected mice with 1 µmol/g sodium l -lactate 1 h or 3 h after permanent middle cerebral artery occlusion (MCAO) and looked at its effect 24 h later. We show a beneficial effect of lactate when administered 1 h after ischemia onset, reducing the lesion size and improving neurological outcome. The weaker effect observed at 3 h could be due to differences in the metabolic profiles related to damage progression. Next, we administered 0.9 mg/kg of intravenous (iv) rtPA, followed by intracerebroventricular injection of 2 µL of 100 mmol/L sodium l -lactate to treat mice subjected to 35-min transient MCAO and compared the outcome (lesion size and behavior) of the combined treatment with that of single treatments. The administration of lactate after rtPA has positive influence on the functional outcome and attenuates the deleterious effects of rtPA, although not as strongly as lactate administered alone. The present work gives a lead for patient selection in future clinical studies of treatment with inexpensive and commonly available lactate in acute ischemic stroke, namely patients not treated with rtPA but mechanical thrombectomy alone or patients without recanalization therapy. |
| first_indexed | 2024-12-13T22:53:04Z |
| format | Article |
| id | doaj.art-205d7227ba7a451786750b38d2704556 |
| institution | Directory Open Access Journal |
| issn | 2514-183X |
| language | English |
| last_indexed | 2024-12-13T22:53:04Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Clinical and Translational Neuroscience |
| spelling | doaj.art-205d7227ba7a451786750b38d27045562022-12-21T23:28:33ZengMDPI AGClinical and Translational Neuroscience2514-183X2020-02-01410.1177/2514183X20904571Extended preclinical investigation of lactate for neuroprotection after ischemic strokeLara Buscemi0Camille Blochet1Melanie Price2Pierre J Magistretti3Hongxia Lei4Lorenz Hirt5 Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland Department of Psychiatry, Lausanne University Hospital Centre and University of Lausanne, Lausanne, Switzerland Center for Biomedical Imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland Department of Fundamental Neurosciences, University of Lausanne, Lausanne, SwitzerlandLactate has been shown to have beneficial effect both in experimental ischemia–reperfusion models and in human acute brain injury patients. To further investigate lactate’s neuroprotective action in experimental in vivo ischemic stroke models prior to its use in clinics, we tested (1) the outcome of lactate administration on permanent ischemia and (2) its compatibility with the only currently approved drug for the treatment of acute ischemic stroke, recombinant tissue plasminogen activator (rtPA), after ischemia–reperfusion. We intravenously injected mice with 1 µmol/g sodium l -lactate 1 h or 3 h after permanent middle cerebral artery occlusion (MCAO) and looked at its effect 24 h later. We show a beneficial effect of lactate when administered 1 h after ischemia onset, reducing the lesion size and improving neurological outcome. The weaker effect observed at 3 h could be due to differences in the metabolic profiles related to damage progression. Next, we administered 0.9 mg/kg of intravenous (iv) rtPA, followed by intracerebroventricular injection of 2 µL of 100 mmol/L sodium l -lactate to treat mice subjected to 35-min transient MCAO and compared the outcome (lesion size and behavior) of the combined treatment with that of single treatments. The administration of lactate after rtPA has positive influence on the functional outcome and attenuates the deleterious effects of rtPA, although not as strongly as lactate administered alone. The present work gives a lead for patient selection in future clinical studies of treatment with inexpensive and commonly available lactate in acute ischemic stroke, namely patients not treated with rtPA but mechanical thrombectomy alone or patients without recanalization therapy.https://doi.org/10.1177/2514183X20904571 |
| spellingShingle | Lara Buscemi Camille Blochet Melanie Price Pierre J Magistretti Hongxia Lei Lorenz Hirt Extended preclinical investigation of lactate for neuroprotection after ischemic stroke Clinical and Translational Neuroscience |
| title | Extended preclinical investigation of lactate for neuroprotection after ischemic stroke |
| title_full | Extended preclinical investigation of lactate for neuroprotection after ischemic stroke |
| title_fullStr | Extended preclinical investigation of lactate for neuroprotection after ischemic stroke |
| title_full_unstemmed | Extended preclinical investigation of lactate for neuroprotection after ischemic stroke |
| title_short | Extended preclinical investigation of lactate for neuroprotection after ischemic stroke |
| title_sort | extended preclinical investigation of lactate for neuroprotection after ischemic stroke |
| url | https://doi.org/10.1177/2514183X20904571 |
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