Image: The MS ESI LC-TOF Micromass LCT 4 (Photo courtesy of Waters / UC Irvine).
Specific small molecules in blood plasma may be useful in determining whether someone has sustained a mild traumatic brain injury (mTBI), commonly known as a concussion.
Such a diagnostic measure would reduce the underreporting of mTBI and allow more appropriate care to be delivered to concussed individuals. In addition, objective biosignatures could provide a basis for temporal assessments that could guide clinical decision-making.
A team of scientists working with their colleagues at University of California, Irvine (Irvine, CA, USA) took blood samples from a subset of 632 athletes entered into contact sports list between 2009 and 2014. Participants were age-, gender-, and sports-matched with teammates who would function as potential control subjects (NC). Season Athletes diagnosed with a mTBI underwent phlebotomy ≤6h post-injury, and then serially at 2 days (2d), 3 days (3d), and 7 days (7d) post-injury, along with their matched NC teammates who served as controls.
Metabolomic analyses were performed in two different batches, on different days, but using the same liquid chromatography–mass spectrometry (LC-MS) equipment. In brief, after sequential extraction untargeted metabolomic profiling of all the plasma specimens was carried out per a previously published protocol. Once putative metabolomic biomarkers are preliminarily annotated, they are either validated or rejected using available or synthesized standards via tandem mass spectrometry (MS/MS) run on randomly selected case and control specimens from the original biomarker discovery cohort. Metabolites confirmed via MS/MS spectral matching are considered fully validated to a high degree of confidence.
The scientists discovered six specific small molecules from blood plasma in a group of college athletes who had been diagnosed with concussions. When these molecules were assessed, their combined presence accurately predicted whether teammates had sustained an mTBI or not. This suggests that these small molecules, and possibly others, might be clinically relevant biomarkers of mTBI. The same six biomarkers were then tested in a separate group of individuals, without and with mTBI, and the results replicated the athlete findings.
Massimo S. Fiandaca, MD, a retired neurosurgeon and a co-author of the study said, “Such blood tests are important in determining not only whether someone has sustained a concussion, which is not currently an easy task, but may eventually prove useful in defining when injured individuals may be eligible to safely return to regular activities.” The study was published on April 20, 2018, in the journal Public Library of Science ONE.
University of California, Irvine