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Temporal proteomics of human cerebrospinal fluid after severe traumatic brain injury
The pathophysiology of traumatic brain injury (TBI) requires further characterization to fully elucidate changes in molecular pathways. Cerebrospinal fluid (CSF) provides a rich repository of brain-associated proteins. In this retrospective observational study, we implemented high-resolution mass sp...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9730674/ https://www.ncbi.nlm.nih.gov/pubmed/36482407 http://dx.doi.org/10.1186/s12974-022-02654-0 |
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author | Shultz, Sandy R. Shah, Anup D. Huang, Cheng Dill, Larissa K. Schittenhelm, Ralf B. Morganti-Kossmann, M. Cristina Semple, Bridgette D. |
author_facet | Shultz, Sandy R. Shah, Anup D. Huang, Cheng Dill, Larissa K. Schittenhelm, Ralf B. Morganti-Kossmann, M. Cristina Semple, Bridgette D. |
author_sort | Shultz, Sandy R. |
collection | PubMed |
description | The pathophysiology of traumatic brain injury (TBI) requires further characterization to fully elucidate changes in molecular pathways. Cerebrospinal fluid (CSF) provides a rich repository of brain-associated proteins. In this retrospective observational study, we implemented high-resolution mass spectrometry to evaluate changes to the CSF proteome after severe TBI. 91 CSF samples were analyzed with mass spectrometry, collected from 16 patients with severe TBI (mean 32 yrs; 81% male) on day 0, 1, 2, 4, 7 and/or 10 post-injury (8–16 samples/timepoint) and compared to CSF obtained from 11 non-injured controls. We quantified 1152 proteins with mass spectrometry, of which approximately 80% were associated with CSF. 1083 proteins were differentially regulated after TBI compared to control samples. The most highly-upregulated proteins at each timepoint included neutrophil elastase, myeloperoxidase, cathepsin G, matrix metalloproteinase-8, and S100 calcium-binding proteins A8, A9 and A12—all proteins involved in neutrophil activation, recruitment, and degranulation. Pathway enrichment analysis confirmed the robust upregulation of proteins associated with innate immune responses. Conversely, downregulated pathways included those involved in nervous system development, and several proteins not previously identified after TBI such as testican-1 and latrophilin-1. We also identified 7 proteins (GM2A, Calsyntenin 1, FAT2, GANAB, Lumican, NPTX1, SFRP2) positively associated with an unfavorable outcome at 6 months post-injury. Together, these findings highlight the robust innate immune response that occurs after severe TBI, supporting future studies to target neutrophil-related processes. In addition, the novel proteins we identified to be differentially regulated by severe TBI warrant further investigation as potential biomarkers of brain damage or therapeutic targets. |
format | Online Article Text |
id | pubmed-9730674 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-97306742022-12-09 Temporal proteomics of human cerebrospinal fluid after severe traumatic brain injury Shultz, Sandy R. Shah, Anup D. Huang, Cheng Dill, Larissa K. Schittenhelm, Ralf B. Morganti-Kossmann, M. Cristina Semple, Bridgette D. J Neuroinflammation Research The pathophysiology of traumatic brain injury (TBI) requires further characterization to fully elucidate changes in molecular pathways. Cerebrospinal fluid (CSF) provides a rich repository of brain-associated proteins. In this retrospective observational study, we implemented high-resolution mass spectrometry to evaluate changes to the CSF proteome after severe TBI. 91 CSF samples were analyzed with mass spectrometry, collected from 16 patients with severe TBI (mean 32 yrs; 81% male) on day 0, 1, 2, 4, 7 and/or 10 post-injury (8–16 samples/timepoint) and compared to CSF obtained from 11 non-injured controls. We quantified 1152 proteins with mass spectrometry, of which approximately 80% were associated with CSF. 1083 proteins were differentially regulated after TBI compared to control samples. The most highly-upregulated proteins at each timepoint included neutrophil elastase, myeloperoxidase, cathepsin G, matrix metalloproteinase-8, and S100 calcium-binding proteins A8, A9 and A12—all proteins involved in neutrophil activation, recruitment, and degranulation. Pathway enrichment analysis confirmed the robust upregulation of proteins associated with innate immune responses. Conversely, downregulated pathways included those involved in nervous system development, and several proteins not previously identified after TBI such as testican-1 and latrophilin-1. We also identified 7 proteins (GM2A, Calsyntenin 1, FAT2, GANAB, Lumican, NPTX1, SFRP2) positively associated with an unfavorable outcome at 6 months post-injury. Together, these findings highlight the robust innate immune response that occurs after severe TBI, supporting future studies to target neutrophil-related processes. In addition, the novel proteins we identified to be differentially regulated by severe TBI warrant further investigation as potential biomarkers of brain damage or therapeutic targets. BioMed Central 2022-12-08 /pmc/articles/PMC9730674/ /pubmed/36482407 http://dx.doi.org/10.1186/s12974-022-02654-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Shultz, Sandy R. Shah, Anup D. Huang, Cheng Dill, Larissa K. Schittenhelm, Ralf B. Morganti-Kossmann, M. Cristina Semple, Bridgette D. Temporal proteomics of human cerebrospinal fluid after severe traumatic brain injury |
title | Temporal proteomics of human cerebrospinal fluid after severe traumatic brain injury |
title_full | Temporal proteomics of human cerebrospinal fluid after severe traumatic brain injury |
title_fullStr | Temporal proteomics of human cerebrospinal fluid after severe traumatic brain injury |
title_full_unstemmed | Temporal proteomics of human cerebrospinal fluid after severe traumatic brain injury |
title_short | Temporal proteomics of human cerebrospinal fluid after severe traumatic brain injury |
title_sort | temporal proteomics of human cerebrospinal fluid after severe traumatic brain injury |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9730674/ https://www.ncbi.nlm.nih.gov/pubmed/36482407 http://dx.doi.org/10.1186/s12974-022-02654-0 |
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