Modeling the Kinetics of Serum Glial Fibrillary Acidic Protein, Ubiquitin Carboxyl-Terminal Hydrolase-L1, and S100B Concentrations in Patients with Traumatic Brain Injury

Abstract

Glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1), and S100B have been shown to be predictive of patients with brain injury. Kinetics of these biomarkers in injured humans have not been extensively examined. This prospective multi-center study included patients with mild-to-moderate traumatic brain injury. Blood samples obtained at enrollment and every 6 h up to 24 h post-injury were assayed for GFAP, UCH-L1, and S100B. Random effects models examined changes in the biomarkers' level over time. A total of 167 patients were enrolled; mean age was 46.0 ± 17.8, 61.1% were male, 143 (85.6%) had a Glasgow Coma Scale score of 15, and 33 (19.8%) had a positive head computed tomography (CT) scan. Baseline median biomarker concentrations for all three were higher among CT-positive patients (p < 0.0001) but GFAP was the only biomarker that significantly increased over time among CT-positive patients relative to CT-negative patients (log transformed values 0.037; 95% confidence interval 0.02, 0.05; p < 0.001), indicating a 3.7% per hour rise in GFAP concentration. There was no significant increase in either UCH-L1 or S100B in CT-positive patients (p = 0.15 and p = 0.47, respectively). GFAP concentrations increased 3.7% per hour among CT-positive patients whereas neither UCH-L1 nor S100B increased, compared with CT-negative patients. The kinetics and temporal profile of GFAP suggest it may be a more robust biomarker to detect patients with positive CT findings, particularly at later post-injury times. Further study is needed to determine if GFAP is a useful test to follow throughout a patient's clinical course.

Serial Sampling of Serum Protein Biomarkers for Monitoring Human Traumatic Brain Injury Dynamics: A Systematic Review

“…Patients suffering from multitrauma and TBI were seen to have higher levels compared to patients with only TBI (11, 48, 92). Generally, the decreasing trajectory of S100B was strongly correlated with the severity of trauma and/or the outcome for the patient (11, 21, 36–38, 41–43, 50, 54, 55, 58, 60, 62, 65, 66, 71, 75, 84, 86, 93–95).…”

“…All different age groups were analyzed, including only or partial pediatric populations (44, 57, 62, 64, 65, 67, 93), even if a vast majority included solely adult patients (7, 11, 18, 21, 34–38, 40–43, 45–51, 53–56, 59–61, 63, 66, 68, 71–92). …”

Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research

“…404 Rapid dynamic changes in biomarker concentrations occur after TBI, and therefore time since injury must be accounted for when using biomarkers as diagnostic or prognostic markers. 405,406 We anticipate a shift from a single-marker approach, which is starting to be implemented in clinical practice, 357 towards compilation of biomarker panels that can be used to overcome diagnostic confounders (eg, extracerebral sources and haemolysis) and avoid the overinterpretation or misinterpretation of information based on a single-marker analysis. 407 Development of a panel of multiple biomarkers that reflect many pathogenic mechanisms holds promise for personalised TBI care.…”

Looking for novel, brain-derived, peripheral biomarkers of neurological disorders

“…In the recent years, a growing interest in the use of UCHL-1 as a serum biomarker for BBB disintegration is observed. After TBI, increased serum UCHL-1 concentrations have been shown [35,36,62,63]. UCHL-1 concentration was elevated in moderate to severe TBI compared to mild TBI patients [35,36,62].…”