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

J Neurotrauma. 2017 Jun 1;34(11):1957-1971. doi: 10.1089/neu.2016.4772. Epub 2017 Feb 27.

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.

Keywords: biomarkers; glia cell response to injury; neural injury; traumatic brain injury.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Brain Injuries, Traumatic / blood*
  • Brain Injuries, Traumatic / diagnostic imaging*
  • Female
  • Glial Fibrillary Acidic Protein / blood*
  • Humans
  • Kinetics
  • Male
  • Middle Aged
  • Prospective Studies
  • S100 Calcium Binding Protein beta Subunit / blood*
  • Tomography, X-Ray Computed / trends
  • Ubiquitin Thiolesterase / blood*

Substances

  • Biomarkers
  • Glial Fibrillary Acidic Protein
  • S100 Calcium Binding Protein beta Subunit
  • S100B protein, human
  • UCHL1 protein, human
  • Ubiquitin Thiolesterase