Cohort Studies; Humans; Metabolome; Metabolomics/methods; Brain Injuries; Brain Injuries, Traumatic; Metabolomics; Chemistry (all); Biochemistry, Genetics and Molecular Biology (all); Physics and Astronomy (all); General Physics and Astronomy; General Biochemistry, Genetics and Molecular Biology; General Chemistry; Multidisciplinary
Abstract :
[en] 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.
Disciplines :
Anesthesia & intensive care
Author, co-author :
Thomas, Ilias; School of Medical Sciences, Örebro University, Örebro, Sweden
Dickens, Alex M; Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland ; Department of Chemistry, University of Turku, Turku, Finland
Posti, Jussi P ; Neurocenter, Department of Neurosurgery and Turku Brain Injury Center, Turku University Hospital and University of Turku, Turku, Finland
Czeiter, Endre ; Department of Neurosurgery, Medical School, University of Pécs, Pécs, Hungary ; Neurotrauma Research Group, Szentágothai Research Centre, University of Pécs, Pécs, Hungary ; MTA-PTE Clinical Neuroscience MR Research Group, Pécs, Hungary
Duberg, Daniel; Department of Chemistry, Örebro University, Örebro, Sweden
Sinioja, Tim; Department of Chemistry, Örebro University, Örebro, Sweden
Kråkström, Matilda; Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
Retel Helmrich, Isabel R A; Department of Public Health, Center for Medical Decision Making, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
Wang, Kevin K W; Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Department of Emergency Medicine, McKnight Brin Institute of the University of Florida, Gainesville, Florida, USA
Maas, Andrew I R ; Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium
Steyerberg, Ewout W ; Department of Public Health, Center for Medical Decision Making, Erasmus MC-University Medical Center, Rotterdam, The Netherlands ; Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
Menon, David K ; Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
Tenovuo, Olli; Neurocenter, Department of Neurosurgery and Turku Brain Injury Center, Turku University Hospital and University of Turku, Turku, Finland
Hyötyläinen, Tuulia; Department of Chemistry, Örebro University, Örebro, Sweden
Büki, András; School of Medical Sciences, Örebro University, Örebro, Sweden ; Department of Neurosurgery, Medical School, University of Pécs, Pécs, Hungary ; Neurotrauma Research Group, Szentágothai Research Centre, University of Pécs, Pécs, Hungary
Orešič, Matej ; School of Medical Sciences, Örebro University, Örebro, Sweden. matej.oresic@oru.se ; Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland. matej.oresic@oru.se
CENTER-TBI was supported by the European Union 7th Framework program (grant no. 602150), with additional project support from OneMind (US), the Hannelore Kohl Foundation (DE), NeuroTrauma Sciences (US), and Integra Neurosciences. The metabolomics study was supported by a grant from Swedish Research Council to M.O. (grant no. 2018-02629). The study was supported by funding from the Academy of Finland to J.P.P. (grant no. 17379), a grant from Government’s Special Financial Transfer tied to academic research in Health Sciences, Finland to J.P.P. (grant no. 11129) a grant from Maire Taponen Foundation to J.P.P. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors thank Daniel Duberg, Lisanna Sinisalu, and Vanja Stefanović for technical assistance in metabolomics analysis and to Dr. Aidan McGlinchey for assistance with language editing. The authors also thank Iftakher Hossain, Janek Frantzén, Mark van Gils, Peter J. Hutchinson, Ari J. Katila, Henna-Riikka Maanpää, Mehrbod Mohammadian, Virginia F. Newcombe, Jussi Tallus and Riikka S.K. Takala (The TBIcare study group).
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