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A Mild Traumatic Brain Injury in Mice Produces Lasting Deficits in Brain Metabolism
Metabolic uncoupling has been well-characterized during the first minutes-to-days after a traumatic brain injury (TBI), yet mitochondrial bioenergetics during the weeks-to-months after a brain injury is poorly defined, particularly after a mild TBI. We hypothesized that a closed head injury (CHI) wo...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Mary Ann Liebert, Inc., publishers
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196750/ https://www.ncbi.nlm.nih.gov/pubmed/29808778 http://dx.doi.org/10.1089/neu.2018.5663 |
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author | Lyons, Danielle N. Vekaria, Hemendra Macheda, Teresa Bakshi, Vikas Powell, David K. Gold, Brian T. Lin, Ai-Ling Sullivan, Patrick G. Bachstetter, Adam D. |
author_facet | Lyons, Danielle N. Vekaria, Hemendra Macheda, Teresa Bakshi, Vikas Powell, David K. Gold, Brian T. Lin, Ai-Ling Sullivan, Patrick G. Bachstetter, Adam D. |
author_sort | Lyons, Danielle N. |
collection | PubMed |
description | Metabolic uncoupling has been well-characterized during the first minutes-to-days after a traumatic brain injury (TBI), yet mitochondrial bioenergetics during the weeks-to-months after a brain injury is poorly defined, particularly after a mild TBI. We hypothesized that a closed head injury (CHI) would be associated with deficits in mitochondrial bioenergetics at one month after the injury. A significant decrease in state-III (adenosine triphosphate production) and state-V (complex-I) driven mitochondrial respiration was found at one month post-injury in adult C57Bl/6J mice. Isolation of synaptic mitochondria demonstrated that the deficit in state-III and state-V was primarily neuronal. Injured mice had a temporally consistent deficit in memory recall at one month post-injury. Using proton magnetic resonance spectroscopy ((1)H MRS) at 7-Tesla, we found significant decreases in phosphocreatine, N-Acetylaspartic acid, and total choline. We also found regional variations in cerebral blood flow, including both hypo- and hyperperfusion, as measured by a pseudocontinuous arterial spin labeling MR sequence. Our results highlight a chronic deficit in mitochondrial bioenergetics associated with a CHI that may lead toward a novel approach for neurorestoration after a mild TBI. MRS provides a potential biomarker for assessing the efficacy of candidate treatments targeted at improving mitochondrial bioenergetics. |
format | Online Article Text |
id | pubmed-6196750 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Mary Ann Liebert, Inc., publishers |
record_format | MEDLINE/PubMed |
spelling | pubmed-61967502018-10-23 A Mild Traumatic Brain Injury in Mice Produces Lasting Deficits in Brain Metabolism Lyons, Danielle N. Vekaria, Hemendra Macheda, Teresa Bakshi, Vikas Powell, David K. Gold, Brian T. Lin, Ai-Ling Sullivan, Patrick G. Bachstetter, Adam D. J Neurotrauma Original Articles Metabolic uncoupling has been well-characterized during the first minutes-to-days after a traumatic brain injury (TBI), yet mitochondrial bioenergetics during the weeks-to-months after a brain injury is poorly defined, particularly after a mild TBI. We hypothesized that a closed head injury (CHI) would be associated with deficits in mitochondrial bioenergetics at one month after the injury. A significant decrease in state-III (adenosine triphosphate production) and state-V (complex-I) driven mitochondrial respiration was found at one month post-injury in adult C57Bl/6J mice. Isolation of synaptic mitochondria demonstrated that the deficit in state-III and state-V was primarily neuronal. Injured mice had a temporally consistent deficit in memory recall at one month post-injury. Using proton magnetic resonance spectroscopy ((1)H MRS) at 7-Tesla, we found significant decreases in phosphocreatine, N-Acetylaspartic acid, and total choline. We also found regional variations in cerebral blood flow, including both hypo- and hyperperfusion, as measured by a pseudocontinuous arterial spin labeling MR sequence. Our results highlight a chronic deficit in mitochondrial bioenergetics associated with a CHI that may lead toward a novel approach for neurorestoration after a mild TBI. MRS provides a potential biomarker for assessing the efficacy of candidate treatments targeted at improving mitochondrial bioenergetics. Mary Ann Liebert, Inc., publishers 2018-10-15 2018-10-01 /pmc/articles/PMC6196750/ /pubmed/29808778 http://dx.doi.org/10.1089/neu.2018.5663 Text en © Danielle N. Lyons et al., 2018; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. |
spellingShingle | Original Articles Lyons, Danielle N. Vekaria, Hemendra Macheda, Teresa Bakshi, Vikas Powell, David K. Gold, Brian T. Lin, Ai-Ling Sullivan, Patrick G. Bachstetter, Adam D. A Mild Traumatic Brain Injury in Mice Produces Lasting Deficits in Brain Metabolism |
title | A Mild Traumatic Brain Injury in Mice Produces Lasting Deficits in Brain Metabolism |
title_full | A Mild Traumatic Brain Injury in Mice Produces Lasting Deficits in Brain Metabolism |
title_fullStr | A Mild Traumatic Brain Injury in Mice Produces Lasting Deficits in Brain Metabolism |
title_full_unstemmed | A Mild Traumatic Brain Injury in Mice Produces Lasting Deficits in Brain Metabolism |
title_short | A Mild Traumatic Brain Injury in Mice Produces Lasting Deficits in Brain Metabolism |
title_sort | mild traumatic brain injury in mice produces lasting deficits in brain metabolism |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196750/ https://www.ncbi.nlm.nih.gov/pubmed/29808778 http://dx.doi.org/10.1089/neu.2018.5663 |
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