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Published Online: 11 January 2016

Circulating Brain-Derived Neurotrophic Factor Has Diagnostic and Prognostic Value in Traumatic Brain Injury

Publication: Journal of Neurotrauma
Volume 33, Issue Number 2

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.

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cover image Journal of Neurotrauma
Journal of Neurotrauma
Volume 33Issue Number 2January 15, 2016
Pages: 215 - 225
PubMed: 26159676

History

Published in print: January 15, 2016
Published online: 11 January 2016
Published ahead of print: 18 September 2015
Published ahead of production: 10 July 2015

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Frederick K. Korley
Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Ramon Diaz-Arrastia
Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
Alan H. B. Wu
Clinical Chemistry Laboratory, San Francisco General Hospital, San Francisco, California.
John K. Yue
Department of Neurological Surgery, University of California San Francisco, San Francisco, California.
Geoffrey T. Manley
Department of Neurological Surgery, University of California San Francisco, San Francisco, California.
Haris I. Sair
Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Jennifer Van Eyk*
Department of Medicine, the Advanced Clinical Biosystems Research Institute, Cedars Sinai Medical Center, Los Angeles, California.
Allen D. Everett*
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
the TRACK-TBI investigators including
David O. Okonkwo
The Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Investigators.
Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Alex B. Valadka
The Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Investigators.
Seton Brain and Spine Institute, Austin, Texas.
Wayne A. Gordon
The Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Investigators.
Department of Rehabilitation Medicine, Mount Sinai School of Medicine, New York, New York.
Andrew I.R. Maas
The Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Investigators.
Department of Neurosurgery, Antwerp University Hospital, Edegem, Belgium.
Pratik Mukherjee
The Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Investigators.
Department of Radiology and Biomedical Imaging University of California San Francisco, San Francisco, California.
Esther L. Yuh
The Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Investigators.
Department of Radiology and Biomedical Imaging University of California San Francisco, San Francisco, California.
Hester F. Lingsma
The Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Investigators.
Department of Public Health Center for Medical Decision Making Erasmas Medical Center, Rotterdam, the Netherlands.
Ava M. Puccio
The Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Investigators.
Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
David M. Schnyer
The Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Investigators.
Department of Psychology, University of Texas, Austin, Texas.

Notes

*
Both authors contributed equally to this publication.
Address correspondence to:Frederick K. Korley, MD, PhDJohns Hopkins University School of MedicineDavis Building, Suite 32205801 Smith AvenueBaltimore, MD 21209E-mail: [email protected]

Author Disclosure Statement

Under a licensing agreement between ImmunArray and the Johns Hopkins University, Drs. Everett, Korley, and Van Eyk are entitled to royalties on an invention described in this article.
This study was supported in part by Grant Numbers RC2NS069409, U01NS086090 from the National Institute of Neurological Disorders and Stroke (NINDS), W81XWH-13-1-0441 from the Department of Defense (DoD) United States Army Medical Research Acquisition Activity, and Contract Number HHSN268201000032C from the National Heart, Lung, and Blood Institute (NHLBI). The contents of this report are solely the responsibility of the authors and do not necessarily represent the official views of the NINDS, DoD, NHLBI, or the National Institute of Health.

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