Citation

Orešič M, Posti JP, Kamstrup-Nielsen MH, Takala RS, Lingsma HF, Mattila I, Jäntti S, Katila AJ, Carpenter KL, Ala-Seppälä H, Kyllönen A, Maanpää HR, Tallus J, Coles JP, Heino I, Frantzén J, Hutchinson PJ, Menon DK, Tenovuo O, Hyötyläinen T. EBioMedicine 2016; 12: 118-126.

Affiliation

Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland; Steno Diabetes Center A/S, DK-2820 Gentofte, Denmark; VTT Technical Research Centre of Finland, FI-02044, VTT, Espoo, Finland; Clinical Research Institute, Helsinki University Central Hospital, FI-00290 Helsinki, Finland; Department of Chemistry, Örebro University, 702 81 Örebro, Sweden. Electronic address: tuulia.hyotylainen@oru.se.

Copyright

(Copyright © 2016, Elsevier Publishing)

DOI

10.1016/j.ebiom.2016.07.015

PMID

27665050

Abstract

Traumatic brain injury (TBI) is a major cause of death and disability worldwide, especially in children and young adults. TBI is an example of a medical condition where there are still major lacks in diagnostics and outcome prediction. Here we apply comprehensive metabolic profiling of serum samples from TBI patients and controls in two independent cohorts. The discovery study included 144 TBI patients, with the samples taken at the time of hospitalization. The patients were diagnosed as severe (sTBI; n=22), moderate (moTBI; n=14) or mild TBI (mTBI; n=108) according to Glasgow Coma Scale. The control group (n=28) comprised of acute orthopedic non-brain injuries. The validation study included sTBI (n=23), moTBI (n=7), mTBI (n=37) patients and controls (n=27). We show that two medium-chain fatty acids (decanoic and octanoic acids) and sugar derivatives including 2,3-bisphosphoglyceric acid are strongly associated with severity of TBI, and most of them are also detected at high concentrations in brain microdialysates of TBI patients. Based on metabolite concentrations from TBI patients at the time of hospitalization, an algorithm was developed that accurately predicted the patient outcomes (AUC=0.84 in validation cohort). Addition of the metabolites to the established clinical model (CRASH), comprising clinical and computed tomography data, significantly improved prediction of patient outcomes. The identified 'TBI metabotype' in serum, that may be indicative of disrupted blood-brain barrier, of protective physiological response and altered metabolism due to head trauma, offers a new avenue for the development of diagnostic and prognostic markers of broad spectrum of TBIs.

Copyright © 2016. Published by Elsevier B.V.

Language: en