Serum metabolome associated with severity of acute traumatic brain injury

Abstract

Complex metabolic disruption is a crucial aspect of the pathophysiology of traumatic brain injury (TBI). Associations between this and systemic metabolism and their potential prognostic value are poorly understood. Here, we aimed to describe the serum metabolome (including lipidome) associated with acute TBI within 24 h post-injury, and its relationship to severity of injury and patient outcome. We performed a comprehensive metabolomics study in a cohort of 716 patients with TBI and non-TBI reference patients (orthopedic, internal medicine, and other neurological patients) from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) cohort. We identified panels of metabolites specifically associated with TBI severity and patient outcomes. Choline phospholipids (lysophosphatidylcholines, ether phosphatidylcholines and sphingomyelins) were inversely associated with TBI severity and were among the strongest predictors of TBI patient outcomes, which was further confirmed in a separate validation dataset of 558 patients. The observed metabolic patterns may reflect different pathophysiological mechanisms, including protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain.

Metadata

Authors/Creators:	Thomas, I. Dickens, A.M. Posti, J.P. https://orcid.org/0000-0002-5925-5193 Czeiter, E. https://orcid.org/0000-0002-9578-6944 Duberg, D. Sinioja, T. Kråkström, M. Retel Helmrich, I.R.A. Wang, K.K.W. Maas, A.I.R. https://orcid.org/0000-0003-1612-1264 Steyerberg, E.W. https://orcid.org/0000-0002-7787-0122 Menon, D.K. https://orcid.org/0000-0002-3228-9692 Tenovuo, O. Hyötyläinen, T. Büki, A. Orešič, M. https://orcid.org/0000-0002-2856-9165 Åkerlund, C. Amrein, K. Andelic, N. Andreassen, L. Anke, A. Antoni, A. Audibert, G. Azouvi, P. Azzolini, M.L. Bartels, R. Barzó, P. Beauvais, R. Beer, R. Bellander, B.-M. Belli, A. Benali, H. Berardino, M. Beretta, L. Blaabjerg, M. Bragge, P. Brazinova, A. Brinck, V. Brooker, J. Brorsson, C. Bullinger, M. Cabeleira, M. Caccioppola, A. Calappi, E. Calvi, M.R. Cameron, P. Lozano, G.C. Carbonara, M. Cavallo, S. Chevallard, G. Chieregato, A. Citerio, G. Clusmann, H. Coburn, M. Coles, J. Cooper, J.D. Correia, M. Čović, A. Curry, N. Czeiter, E. Czosnyka, M. Dahyot-Fizelier, C. Dark, P. Dawes, H. De Keyser, V. Degos, V. Corte, F.D. den Boogert, H. Depreitere, B. Đilvesi, Đ Dixit, A. Donoghue, E. Dreier, J. Dulière, G.-L. Ercole, A. Esser, P. Ezer, E. Fabricius, M. Feigin, V.L. Foks, K. Frisvold, S. Furmanov, A. Gagliardo, P. Galanaud, D. Gantner, D. Gao, G. George, P. Ghuysen, A. Giga, L. Glocker, B. Golubovic, J. Gomez, P.A. Gratz, J. Gravesteijn, B. Grossi, F. Gruen, R.L. Gupta, D. Haagsma, J.A. Haitsma, I. Helbok, R. Helseth, E. Horton, L. Huijben, J. Hutchinson, P.J. Jacobs, B. Jankowski, S. Jarrett, M. Jiang, J.-Y. Johnson, F. Jones, K. Karan, M. Kolias, A.G. Kompanje, E. Kondziella, D. Kornaropoulos, E. Koskinen, L.-O. Kovács, N. Kowark, A. Lagares, A. Lanyon, L. Laureys, S. Lecky, F. https://orcid.org/0000-0001-6806-0921 Ledoux, D. Lefering, R. Legrand, V. Lejeune, A. Levi, L. Lightfoot, R. Lingsma, H. Maas, A.I.R. Castaño-León, A.M. Maegele, M. Majdan, M. Manara, A. Manley, G. Martino, C. Maréchal, H. Mattern, J. McMahon, C. Melegh, B. Menovsky, T. Mikolic, A. Misset, B. Muraleedharan, V. Murray, L. Negru, A. Nelson, D. Newcombe, V. Nieboer, D. Nyirádi, J. Olubukola, O. Ortolano, F. Palotie, A. Parizel, P.M. Payen, J.-F. Perera, N. Perlbarg, V. Persona, P. Peul, W. Piippo-Karjalainen, A. Pirinen, M. Ples, H. Polinder, S. Pomposo, I. Posti, J.P. Puybasset, L. Radoi, A. Ragauskas, A. Raj, R. Rambadagalla, M. Rhodes, J. Richardson, S. Richter, S. Ripatti, S. Rocka, S. Roe, C. Roise, O. Rosand, J. Rosenfeld, J.V. Rosenlund, C. Rosenthal, G. Rossaint, R. Rossi, S. Rueckert, D. Rusnák, M. Sahuquillo, J. Sakowitz, O. Sanchez-Porras, R. Sandor, J. Schäfer, N. Schmidt, S. Schoechl, H. Schoonman, G. Schou, R.F. Schwendenwein, E. Sewalt, C. Skandsen, T. Smielewski, P. Sorinola, A. Stamatakis, E. Stanworth, S. Stevens, R. Stewart, W. Stocchetti, N. Sundström, N. Takala, R. Tamás, V. Tamosuitis, T. Taylor, M.S. Te Ao, B. Theadom, A. Thomas, M. Tibboel, D. Timmers, M. Tolias, C. Trapani, T. Tudora, C.M. Unterberg, A. Vajkoczy, P. Vallance, S. Valeinis, E. Vámos, Z. van der Jagt, M. Van der Steen, G. van der Naalt, J. van Dijck, J.T.J.M. van Essen, T.A. Van Hecke, W. van Heugten, C. Van Praag, D. Vyvere, T.V. van Wijk, R.P.J. Vargiolu, A. Vega, E. Velt, K. Verheyden, J. Vespa, P.M. Vik, A. Vilcinis, R. Volovici, V. von Steinbüchel, N. Voormolen, D. Vulekovic, P. Wiegers, E. Williams, G. Wilson, L. Winzeck, S. Wolf, S. Yang, Z. Ylén, P. Younsi, A. Zeiler, F.A. Zelinkova, V. Ziverte, A. Zoerle, T.
Copyright, Publisher and Additional Information:	© The Author(s) 2022. This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords:	Brain Injuries; Brain Injuries, Traumatic; Cohort Studies; Humans; Metabolome; Metabolomics
Dates:	Accepted: 21 April 2022 Published (online): 10 May 2022 Published: 10 May 2022
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health
Depositing User:	Symplectic Sheffield
Date Deposited:	24 Jan 2024 16:10
Last Modified:	24 Jan 2024 16:10
Published Version:	http://dx.doi.org/10.1038/s41467-022-30227-5
Status:	Published
Publisher:	Springer Science and Business Media LLC
Refereed:	Yes
Identification Number:	https://doi.org/10.1038/s41467-022-30227-5
Related URLs:	PubMed URL

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Serum metabolome associated with severity of acute traumatic brain injury

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