Elucidating the Metabolomic Profile of Recovery from Traumatic Brain Injury
Although mild traumatic brain injury (mTBI) affects an estimated 1.8-3.6 million persons each year, no diagnostic tools exist for evaluating this injury. Evaluation of mTBI relies on accurate history taking (dependent on patient’s recollection) and physical examination (not always reliable). The majority of concussed persons achieve full recovery within 7 days, however, approximately 25% have persistent cognitive deficits that last more than 30 days.
Unfortunately, clinicians have no objective tools for predicting how long it will take for a concussed person to recover. Additionally, there are no pharmacologic treatments for mTBI. Current efforts to identify blood-based biomarkers for predicting protracted recovery from mTBI are focused on examining circulating proteins (proteomics).
However, the existence of the blood brain barrier (BBB) limits the ability of brain-enriched proteins (which are typically large) to enter the circulatory system. Therefore innovative approaches are needed for identifying novel blood-based biomarkers of mTBI. Metabolomics is a newly emerging scientific field focused on the identification and measurement of metabolites in biological samples by either high-throughput mass spectroscopy or nuclear magnetic resonance NMR spectroscopy. Metabolites are small molecule intermediates and products of cellular metabolism.
Recent advances in biotechnology fused with “big data” analytics now allow the measurement of large numbers of metabolites over a short period of time. This advance has helped unravel mechanisms underlining different diseases and has led to the identification of blood-based biomarkers of cardiovascular disease and oncology, among others. Since metabolites are smaller than proteins they are more likely to cross the BBB and thus can provide a window into pathological processes occurring in the brain. We hypothesize that differences between the metabolome of concussed persons achieving full recovery and those with protracted recovery will provide insights into the biology of recovery and yield novel biomarkers for predicting protracted recovery and targets for therapeutic intervention.