Serum Metabolites Associated with Traumatic Brain Injury Severity

Traumatic brain injury (TBI) is a major cause of death and disability worldwide, especially in children and young adults and is an example of a medical condition where there are still major deficits in diagnostics and outcome prediction.

Since the blood-brain barrier prevents diffusion of most water-soluble molecules with molecular mass over 500 dalton (Da), it hs been hypothesized that circulating small molecules or metabolites are a potential source of TBI biomarkers.


Biotechnologists from the University of Turku (Finland) and their colleagues prospectively recruited total of 389 adult patients with acute TBI and 81 patients with acute orthopedic trauma without acute or previous brain disorders, who served as controls and another 211 patients with acute TBI and 55 orthopedic trauma patients who had eligible serum samples available from a hospital in the UK. Blood samples of 2 mL for metabolomic analysis were collected within 12 hours after hospital admission.

Two-Dimensional Gas Chromatography with Time-of-Flight Mass Spectrometer (GC × GC–TOFMS) analyses were carried out on an Agilent 6890 gas chromatograph equipped with a split/splitless injector (Agilent Technologies, Santa Clara, CA, USA), cryogenic dual-stage modulator and time-of-flight mass spectrometer (Leco Corporation, St. Joseph, MI, USA).

The scientists discovered 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 (area under the curve (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 authors concluded that TBI is associated with a specific metabolic profile, which is exacerbated proportionally to the severity of TBI. High degree of concentration changes of TBI metabolites in serum as well as their proportional enrichment in brain microdialysate (BMD) is indicative of multiple underlying mechanisms including potential disruption in the blood brain barrier as well as protective response and altered metabolism due to head trauma. These findings also suggest that these metabolites may exhibit diagnostic potential in the full spectrum of TBI. The study was published originally online on July 15, 2016, as is now an article in press in the journal EbioMedicine.

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University of Turku
Agilent Technologies
Leco