title: Circulating Brain-Derived Neurotrophic Factor Has Diagnostic and Prognostic Value in Traumatic Brain Injury.
abstract: Brain-derived neurotrophic factor (BDNF) is important for neuronal survival and regeneration. We investigated the diagnostic and prognostic values of serum BDNF in traumatic brain injury (TBI). We examined serum BDNF in two independent cohorts of TBI cases presenting to the emergency departments (EDs) of the Johns Hopkins Hospital (JHH; n = 76) and San Francisco General Hospital (SFGH, n = 80), and a control group of JHH ED patients without TBI (n = 150). Findings were subsequently validated in the prospective, multi-center Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Pilot study (n = 159). We investigated the association between BDNF, glial fibrillary acidic protein (GFAP), and ubiquitin C-terminal hydrolase-L1 (UCH-L1) and recovery from TBI at 6 months in the TRACK-TBI Pilot cohort. Incomplete recovery was defined as having either post-concussive syndrome or a Glasgow Outcome Scale Extended score <8 at 6 months. Median day-of-injury BDNF concentrations (ng/mL) were lower among TBI cases (JHH TBI, 17.5 and SFGH TBI, 13.8) than in JHH controls (60.3; p = 0.0001). Among TRACK-TBI Pilot subjects, median BDNF concentrations (ng/mL) were higher in mild (8.3) than in moderate (4.3) or severe TBI (4.0; p = 0.004. In the TRACK-TBI cohort, the 75 (71.4%) subjects with very low BDNF values (i.e., <the 1st percentile for non-TBI controls, <14.2 ng/mL) had higher odds of incomplete recovery than those who did not have very low values (odds ratio, 4.0; 95% confidence interval [CI]: 1.5-11.0). The area under the receiver operator curve for discriminating complete and incomplete recovery was 0.65 (95% CI: 0.52-0.78) for BDNF, 0.61 (95% CI: 0.49-0.73) for GFAP, and 0.55 (95% CI: 0.43-0.66) for UCH-L1. The addition of GFAP/UCH-L1 to BDNF did not improve outcome prediction significantly. Day-of-injury serum BDNF is associated with TBI diagnosis and also provides 6-month prognostic information regarding recovery from TBI. Thus, day-of-injury BDNF values may aid in TBI risk stratification.
authors.affiliation: 1 Department of Emergency Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Frederick K
authors.initials: FK
authors.lastname: Korley
authors.affiliation: 2 Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences , Bethesda, Maryland.
authors.forename: Ramon
authors.initials: R
authors.lastname: Diaz-Arrastia
authors.affiliation: 3 Clinical Chemistry Laboratory, San Francisco General Hospital , San Francisco, California.
authors.forename: Alan H B
authors.initials: AH
authors.lastname: Wu
authors.affiliation: 4 Department of Neurological Surgery, University of California San Francisco , San Francisco, California.
authors.forename: John K
authors.initials: JK
authors.lastname: Yue
authors.affiliation: 4 Department of Neurological Surgery, University of California San Francisco , San Francisco, California.
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: Manley
authors.affiliation: 5 Department of Radiology, Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Haris I
authors.initials: HI
authors.lastname: Sair
authors.affiliation: 6 Department of Medicine, the Advanced Clinical Biosystems Research Institute , Cedars Sinai Medical Center, Los Angeles, California.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Van Eyk
authors.affiliation: 7 Department of Pediatrics, Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Allen D
authors.initials: AD
authors.lastname: Everett
authors.affiliation: 8 The Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Investigators .|9 Department of Neurological Surgery, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.
authors.forename: David O
authors.initials: DO
authors.lastname: Okonkwo
authors.affiliation: 8 The Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Investigators .|10 Seton Brain and Spine Institute , Austin, Texas.
authors.forename: Alex B
authors.initials: AB
authors.lastname: Valadka
authors.affiliation: 8 The Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Investigators .|11 Department of Rehabilitation Medicine, Mount Sinai School of Medicine , New York, New York.
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Gordon
authors.affiliation: 8 The Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Investigators .|12 Department of Neurosurgery, Antwerp University Hospital , Edegem, Belgium .
authors.forename: Andrew I R
authors.initials: AI
authors.lastname: Maas
authors.affiliation: 8 The Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Investigators .|13 Department of Radiology and Biomedical Imaging University of California San Francisco , San Francisco, California.
authors.forename: Pratik
authors.initials: P
authors.lastname: Mukherjee
authors.affiliation: 8 The Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Investigators .|13 Department of Radiology and Biomedical Imaging University of California San Francisco , San Francisco, California.
authors.forename: Esther L
authors.initials: EL
authors.lastname: Yuh
authors.affiliation: 8 The Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Investigators .|14 Department of Public Health Center for Medical Decision Making Erasmas Medical Center , Rotterdam, the Netherlands .
authors.forename: Hester F
authors.initials: HF
authors.lastname: Lingsma
authors.affiliation: 8 The Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Investigators .|9 Department of Neurological Surgery, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.
authors.forename: Ava M
authors.initials: AM
authors.lastname: Puccio
authors.affiliation: 8 The Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Investigators .|15 Department of Psychology, University of Texas , Austin, Texas.
authors.forename: David M
authors.initials: DM
authors.lastname: Schnyer
mesh_terms: D000328:Adult; D001930:Brain Injuries / Q000097:blood*; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010865:Pilot Projects; D011446:Prospective Studies; D011897:Random Allocation; D020127:Recovery of Function / Q000502:physiology*; D012720:Severity of Illness Index
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
keywords: biomarkers; brain-derived neurotrophic factor; glial fibrillary acidic protein; traumatic brain injury; ubiquitin C-terminal hydrolase-L1