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Combined Treatment With Dichloroacetic Acid and Pyruvate Reduces Hippocampal Neuronal Death After Transient Cerebral Ischemia

Transient cerebral ischemia (TCI) occurs when blood flow to the brain is ceased or dramatically reduced. TCI causes energy depletion and oxidative stress, which leads to neuronal death and cognitive impairment. Dichloroacetic acid (DCA) acts as an inhibitor of pyruvate dehydrogenase kinase (PDK). Ad...

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Autores principales: Hong, Dae Ki, Kho, A Ra, Choi, Bo Young, Lee, Song Hee, Jeong, Jeong Hyun, Lee, Sang Hwon, Park, Kyoung-Ha, Park, Jae-Bong, Suh, Sang Won
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5857568/
https://www.ncbi.nlm.nih.gov/pubmed/29593636
http://dx.doi.org/10.3389/fneur.2018.00137
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author Hong, Dae Ki
Kho, A Ra
Choi, Bo Young
Lee, Song Hee
Jeong, Jeong Hyun
Lee, Sang Hwon
Park, Kyoung-Ha
Park, Jae-Bong
Suh, Sang Won
author_facet Hong, Dae Ki
Kho, A Ra
Choi, Bo Young
Lee, Song Hee
Jeong, Jeong Hyun
Lee, Sang Hwon
Park, Kyoung-Ha
Park, Jae-Bong
Suh, Sang Won
author_sort Hong, Dae Ki
collection PubMed
description Transient cerebral ischemia (TCI) occurs when blood flow to the brain is ceased or dramatically reduced. TCI causes energy depletion and oxidative stress, which leads to neuronal death and cognitive impairment. Dichloroacetic acid (DCA) acts as an inhibitor of pyruvate dehydrogenase kinase (PDK). Additionally, DCA is known to increase mitochondrial pyruvate uptake and promotes glucose oxidation during glycolysis, thus enhancing pyruvate dehydrogenase (PDH) activity. In this study, we investigated whether the inhibition of PDK activity by DCA, which increases the rate of pyruvate conversion to adenosine triphosphate (ATP), prevents ischemia-induced neuronal death. We used a rat model of TCI, which was induced by common carotid artery occlusion and hypovolemia for 7 min while monitoring the electroencephalography for sustained isoelectric potential. Male Sprague-Dawley rats were given an intraperitoneal injection of DCA (100 mg/kg) with pyruvate (50 mg/kg) once per day for 2 days after insult. The vehicle, DCA only or pyruvate on rats was injected on the same schedule. Our study demonstrated that the combined administration of DCA with pyruvate significantly decreased neuronal death, oxidative stress, microglia activation when compared with DCA, or pyruvate injection alone. These findings suggest that the administration of DCA with pyruvate may enhance essential metabolic processes, which in turn promotes the regenerative capacity of the post-ischemic brain.
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spelling pubmed-58575682018-03-28 Combined Treatment With Dichloroacetic Acid and Pyruvate Reduces Hippocampal Neuronal Death After Transient Cerebral Ischemia Hong, Dae Ki Kho, A Ra Choi, Bo Young Lee, Song Hee Jeong, Jeong Hyun Lee, Sang Hwon Park, Kyoung-Ha Park, Jae-Bong Suh, Sang Won Front Neurol Neuroscience Transient cerebral ischemia (TCI) occurs when blood flow to the brain is ceased or dramatically reduced. TCI causes energy depletion and oxidative stress, which leads to neuronal death and cognitive impairment. Dichloroacetic acid (DCA) acts as an inhibitor of pyruvate dehydrogenase kinase (PDK). Additionally, DCA is known to increase mitochondrial pyruvate uptake and promotes glucose oxidation during glycolysis, thus enhancing pyruvate dehydrogenase (PDH) activity. In this study, we investigated whether the inhibition of PDK activity by DCA, which increases the rate of pyruvate conversion to adenosine triphosphate (ATP), prevents ischemia-induced neuronal death. We used a rat model of TCI, which was induced by common carotid artery occlusion and hypovolemia for 7 min while monitoring the electroencephalography for sustained isoelectric potential. Male Sprague-Dawley rats were given an intraperitoneal injection of DCA (100 mg/kg) with pyruvate (50 mg/kg) once per day for 2 days after insult. The vehicle, DCA only or pyruvate on rats was injected on the same schedule. Our study demonstrated that the combined administration of DCA with pyruvate significantly decreased neuronal death, oxidative stress, microglia activation when compared with DCA, or pyruvate injection alone. These findings suggest that the administration of DCA with pyruvate may enhance essential metabolic processes, which in turn promotes the regenerative capacity of the post-ischemic brain. Frontiers Media S.A. 2018-03-12 /pmc/articles/PMC5857568/ /pubmed/29593636 http://dx.doi.org/10.3389/fneur.2018.00137 Text en Copyright © 2018 Hong, Kho, Choi, Lee, Jeong, Lee, Park, Park and Suh. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Hong, Dae Ki
Kho, A Ra
Choi, Bo Young
Lee, Song Hee
Jeong, Jeong Hyun
Lee, Sang Hwon
Park, Kyoung-Ha
Park, Jae-Bong
Suh, Sang Won
Combined Treatment With Dichloroacetic Acid and Pyruvate Reduces Hippocampal Neuronal Death After Transient Cerebral Ischemia
title Combined Treatment With Dichloroacetic Acid and Pyruvate Reduces Hippocampal Neuronal Death After Transient Cerebral Ischemia
title_full Combined Treatment With Dichloroacetic Acid and Pyruvate Reduces Hippocampal Neuronal Death After Transient Cerebral Ischemia
title_fullStr Combined Treatment With Dichloroacetic Acid and Pyruvate Reduces Hippocampal Neuronal Death After Transient Cerebral Ischemia
title_full_unstemmed Combined Treatment With Dichloroacetic Acid and Pyruvate Reduces Hippocampal Neuronal Death After Transient Cerebral Ischemia
title_short Combined Treatment With Dichloroacetic Acid and Pyruvate Reduces Hippocampal Neuronal Death After Transient Cerebral Ischemia
title_sort combined treatment with dichloroacetic acid and pyruvate reduces hippocampal neuronal death after transient cerebral ischemia
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5857568/
https://www.ncbi.nlm.nih.gov/pubmed/29593636
http://dx.doi.org/10.3389/fneur.2018.00137
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