title: 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.
authors.affiliation: 1 Department of Emergency Medicine, Wayne State University School of Medicine , Detroit, Michigan.|2 Cardiovascular Research Institute, Wayne State University School of Medicine , Detroit, Michigan.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Welch
authors.affiliation: 1 Department of Emergency Medicine, Wayne State University School of Medicine , Detroit, Michigan.
authors.forename: Morgan
authors.initials: M
authors.lastname: Ellis
authors.affiliation: 3 Department of Emergency Medicine, Washington University School of Medicine , St. Louis, Missouri.
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Lewis
authors.affiliation: 1 Department of Emergency Medicine, Wayne State University School of Medicine , Detroit, Michigan.
authors.forename: Syed I
authors.initials: SI
authors.lastname: Ayaz
authors.affiliation: 1 Department of Emergency Medicine, Wayne State University School of Medicine , Detroit, Michigan.
authors.forename: Valerie H
authors.initials: VH
authors.lastname: Mika
authors.affiliation: 1 Department of Emergency Medicine, Wayne State University School of Medicine , Detroit, Michigan.|4 Department of Physical Medicine and Rehabilitation, Wayne State University School of Medicine , Detroit, Michigan.
authors.forename: Scott
authors.initials: S
authors.lastname: Millis
authors.affiliation: 5 Department of Emergency Medicine, Orlando Regional Medical Center , Orlando, Florida.
authors.forename: Linda
authors.initials: L
authors.lastname: Papa
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D000070642:Brain Injuries, Traumatic / Q000097:blood* / Q000000981:diagnostic imaging*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000097:blood*; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood*; D014057:Tomography, X-Ray Computed / Q000639:trends; D043222:Ubiquitin Thiolesterase / Q000097:blood*
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase
keywords: biomarkers; glia cell response to injury; neural injury; traumatic brain injury