Metabolomics and Biomarker Discovery in Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) is one of the leading causes of disability and mortality worldwide. The TBI pathogenesis can induce broad pathophysiological consequences and clinical outcomes attributed to the complexity of the brain. Thus, the diagnosis and prognosis are important issues for the management of mild, moderate, and severe forms of TBI. Metabolomics of readily accessible biofluids is a promising tool for establishing more useful and reliable biomarkers of TBI than using clinical findings alone. Metabolites are an integral part of all biochemical and pathophysiological pathways. Metabolomic processes respond to the internal and external stimuli resulting in an alteration of metabolite concentrations. Current high-throughput and highly sensitive analytical tools are capable of detecting and quantifying small concentrations of metabolites, allowing one to measure metabolite alterations after a pathological event when compared to a normal state or a different pathological process. Further, these metabolic biomarkers could be used for the assessment of injury severity, discovery of mechanisms of injury, and defining structural damage in the brain in TBI. Metabolic biomarkers can also be used for the prediction of outcome, monitoring treatment response, in the assessment of or prognosis of post-injury recovery, and potentially in the use of neuroplasticity procedures. Metabolomics can also enhance our understanding of the pathophysiological mechanisms of TBI, both in primary and secondary injury. Thus, this review presents the promising application of metabolomics for the assessment of TBI as a stand-alone platform or in association with proteomics in the clinical setting.

Head trauma in sports – clinical characteristics, epidemiology and biomarkers

“…Metabolomics is a fairly new area in biomedicine, which analyses these substances as potential biomarkers of ongoing metabolic processes. Metabolite biomarkers have some special advantages in brain research over the more conventional protein biomarkers : as small molecules they are less dependent on the blood‐brain‐barrier, they usually react more quickly on (patho)physiological phenomena, and they can describe simultaneously an array of concomitant processes. As shortcomings, they are usually not organ‐specific; they are influenced by external factors, such as diet, exercise and medications, and their origin may be difficult to ascertain.…”

Metabolomics in postmortem cerebrospinal fluid diagnostics: a state-of-the-art method to interpret central nervous system–related pathological processes

“…Furthermore, since metabolomics is a promising technique for mapping the brain, multivariate analysis indicated significant differences between brain areas (cerebellum, brain stem, thalamus, frontal cortex, and ventral cortex). The brain regions with high interaction showed more similarity in metabolite signatures [6,48]. If these imbalances are also represented in CSF of different locations is undetermined to date.…”

“…With the help of metabolite profiles in biological specimens, physicians are able to understand pathophysiological mechanisms-such as the development of diseases or the traumatization of tissue [6]-at the biochemical and thus the functional level. An additional advantage of this approach is that the metabolites and metabolic pathways of amino acids, carbohydrates, and lipids are already known and can be analyzed using automated procedures [7].…”

Secreted Peptides for Diagnostic Trajectory Assessments in Brain Injury Rehabilitation

“…Results here capitalized on recent advancements in peptidomic assessment with data-independent mass spectrometry, a robust means to quantify endogenous peptides excreted into urine, and an optimal approach for developing biomarker assays in complex injury. 14 Urine provides a noninvasive, readily-collectable medium for diagnostic use across inpatient and outpatient settings. 13,52 Urine is moreover enriched in secreted byproducts of ongoing pathobiology that are not attenuated by homeostatic mechanisms and has less lipid and proteinaceous interferants than blood.…”

“…8 Yet the application of omic mass spectrometry to TBI diagnostics has largely been limited to studying the acute-phase response. 12,14 TBI pathophysiology underlying secondary sequelae continues to evolve in the postacute period, 8 warranting discrete biomarker assays to inform on patient progress during rehabilitation and portend future recovery. 11…”