Panel of serum protein biomarkers to grade the severity of traumatic brain injury

Abstract

The Glasgow Coma Scale (GCS), which classifies patients into mild, moderate or severe traumatic brain injury (TBI), is a system used to prioritize treatment and prognosticate the severity of head injury. In this study, sera of patients with various stages of TBI, as well as control subjects, were analyzed to screen for proteins that may be used to complement the GCS system. By subjecting pooled serum samples to iTRAQ analysis for quantitative comparison of protein abundance, and attesting their altered levels using ELISA, we have detected increased levels of serum amyloid A, C-reactive protein, leucine-rich alpha-2-glycoprotein, lipopolysaccharide-binding protein, fibronectin, vitronectin and alpha-1-antichymotrypsin in patients across all strata of TBI relative to the controls. However, kininogen was decreased only in moderate and severe TBI, whereas apolipoprotein E and zinc-alpha-2-glycoprotein were only increased in severe TBI. Hence, we propose a panel of serum biomarkers, which if analyzed within 24 h of the injury, can be used to diagnose patients with TBI into mild, moderate or severe stratification objectively, thus complementing the traditional GCS.

The good, the bad, and the opportunities of the complement system in neurodegenerative disease

“…Therefore, the window between the initial TBI and secondary injury is critical for prognosis and preventative treatment [251]. The Glasgow coma scale (GCS) has been the primary measure of severity; however, this scale is imperfect at determining prognosis, and occluding factors (such as sedation or alcohol consumption) can interfere with test results [252]. Therefore, much effort has been placed on identifying biomarkers specific for different severities of TBI.…”

“…Whereas C3a levels immediately peak in the serum after TBI and remain elevated, C5a levels are increased immediately after injury but continue to rise substantially up to 10 days after initial injury [212]. A recent panel of serum-derived proteins from patients with mild, moderate, and severe TBI revealed proteins that are elevated in all levels of TBI compared with control subjects (serum amyloid A, C-reactive protein, LPSbinding protein), proteins that are downregulated in moderate and severe TBI compared with mild TBI and controls (kininogen), and proteins that are upregulated only in severe TBI cases (apolipoprotein E and zinc alpha-2 glycoprotein) [252]. Analysis of CSF may provide more accurate biomarkers for trauma in the brain.…”

Proteomic changes in traumatic brain injury: experimental approaches

“…Anada et al [ 7 ▪ ] proposed a panel of human serum protein biomarkers to measure the severity of TBI. Although patients with TBI are traditionally stratified based upon the Glasgow Coma Scale (GCS), the authors argued that the increased use prior to arrival at the hospital of intubation and sedation, would eliminate verbal responses and may eliminate eye opening (two of the three components of the GCS), impair assessment of patient status, and could increase the importance of serum biomarkers.…”

Quantitative proteomic characterization of microvesicles/exosomes from the cerebrospinal fluid of patients with acute bilirubin encephalopathy

“…in a previous study, aPP protein was demonstrated to induce a predominantly proinflammatory phenotype of microglia in Alzheimer's disease (41). Moreover, LBP and CRP, which are non-specific markers of inflammation, were found to be significantly increased in the serum of patients with traumatic brain injury (42,43). although these non-specific immune-inflammatory markers have been studied in the context of traumatic brain injury and neurodegenerative diseases, to the best of our knowledge, their role in the context of ucB-induced neurological dysfunction is not well characterized.…”