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Scaled traumatic brain injury results in unique metabolomic signatures between gray matter, white matter, and serum in a piglet model
Traumatic brain injury (TBI) is a leading cause of death and long-term disability in the United States. The heterogeneity of the disease coupled with the lack of comprehensive, standardized scales to adequately characterize multiple types of TBI remain to be major challenges facing effective therape...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209298/ https://www.ncbi.nlm.nih.gov/pubmed/30379914 http://dx.doi.org/10.1371/journal.pone.0206481 |
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author | Baker, Emily W. Henderson, W. Matthew Kinder, Holly A. Hutcheson, Jessica M. Platt, Simon R. West, Franklin D. |
author_facet | Baker, Emily W. Henderson, W. Matthew Kinder, Holly A. Hutcheson, Jessica M. Platt, Simon R. West, Franklin D. |
author_sort | Baker, Emily W. |
collection | PubMed |
description | Traumatic brain injury (TBI) is a leading cause of death and long-term disability in the United States. The heterogeneity of the disease coupled with the lack of comprehensive, standardized scales to adequately characterize multiple types of TBI remain to be major challenges facing effective therapeutic development. A systems level approach to TBI diagnosis through the use of metabolomics could lead to a better understanding of cellular changes post-TBI and potential therapeutic targets. In the current study, we utilize a GC-MS untargeted metabolomics approach to demonstrate altered metabolism in response to TBI in a translational pig model, which possesses many neuroanatomical and pathophysiologic similarities to humans. TBI was produced by controlled cortical impact (CCI) in Landrace piglets with impact velocity and depth of depression set to 2m/s;6mm, 4m/s;6mm, 4m/s;12mm, or 4m/s;15mm resulting in graded neural injury. Serum samples were collected pre-TBI, 24 hours post-TBI, and 7 days post-TBI. Partial least squares discriminant analysis (PLS-DA) revealed that each impact parameter uniquely influenced the metabolomic profile after TBI, and gray and white matter responds differently to TBI on the biochemical level with evidence of white matter displaying greater metabolic change. Furthermore, pathway analysis revealed unique metabolic signatures that were dependent on injury severity and brain tissue type. Metabolomic signatures were also detected in serum samples which potentially captures both time after injury and injury severity. These findings provide a platform for the development of a more accurate TBI classification scale based unique metabolomic signatures. |
format | Online Article Text |
id | pubmed-6209298 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-62092982018-11-19 Scaled traumatic brain injury results in unique metabolomic signatures between gray matter, white matter, and serum in a piglet model Baker, Emily W. Henderson, W. Matthew Kinder, Holly A. Hutcheson, Jessica M. Platt, Simon R. West, Franklin D. PLoS One Research Article Traumatic brain injury (TBI) is a leading cause of death and long-term disability in the United States. The heterogeneity of the disease coupled with the lack of comprehensive, standardized scales to adequately characterize multiple types of TBI remain to be major challenges facing effective therapeutic development. A systems level approach to TBI diagnosis through the use of metabolomics could lead to a better understanding of cellular changes post-TBI and potential therapeutic targets. In the current study, we utilize a GC-MS untargeted metabolomics approach to demonstrate altered metabolism in response to TBI in a translational pig model, which possesses many neuroanatomical and pathophysiologic similarities to humans. TBI was produced by controlled cortical impact (CCI) in Landrace piglets with impact velocity and depth of depression set to 2m/s;6mm, 4m/s;6mm, 4m/s;12mm, or 4m/s;15mm resulting in graded neural injury. Serum samples were collected pre-TBI, 24 hours post-TBI, and 7 days post-TBI. Partial least squares discriminant analysis (PLS-DA) revealed that each impact parameter uniquely influenced the metabolomic profile after TBI, and gray and white matter responds differently to TBI on the biochemical level with evidence of white matter displaying greater metabolic change. Furthermore, pathway analysis revealed unique metabolic signatures that were dependent on injury severity and brain tissue type. Metabolomic signatures were also detected in serum samples which potentially captures both time after injury and injury severity. These findings provide a platform for the development of a more accurate TBI classification scale based unique metabolomic signatures. Public Library of Science 2018-10-31 /pmc/articles/PMC6209298/ /pubmed/30379914 http://dx.doi.org/10.1371/journal.pone.0206481 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
spellingShingle | Research Article Baker, Emily W. Henderson, W. Matthew Kinder, Holly A. Hutcheson, Jessica M. Platt, Simon R. West, Franklin D. Scaled traumatic brain injury results in unique metabolomic signatures between gray matter, white matter, and serum in a piglet model |
title | Scaled traumatic brain injury results in unique metabolomic signatures between gray matter, white matter, and serum in a piglet model |
title_full | Scaled traumatic brain injury results in unique metabolomic signatures between gray matter, white matter, and serum in a piglet model |
title_fullStr | Scaled traumatic brain injury results in unique metabolomic signatures between gray matter, white matter, and serum in a piglet model |
title_full_unstemmed | Scaled traumatic brain injury results in unique metabolomic signatures between gray matter, white matter, and serum in a piglet model |
title_short | Scaled traumatic brain injury results in unique metabolomic signatures between gray matter, white matter, and serum in a piglet model |
title_sort | scaled traumatic brain injury results in unique metabolomic signatures between gray matter, white matter, and serum in a piglet model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209298/ https://www.ncbi.nlm.nih.gov/pubmed/30379914 http://dx.doi.org/10.1371/journal.pone.0206481 |
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