Circulating Brain Derived Neurotrophic Factor (BDNF

Journal of Neurotrauma Circulating Brain Derived Neurotrophic Factor (BDNF) Has Diagnostic and Prognostic Value in Traumatic Brain Injury. (doi: 10.1089/neu.2015.3949) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.

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1 Full Title: Circulating Brain Derived Neurotrophic Factor (BDNF) Has Diagnostic and Prognostic Value in Traumatic Brain Injury. Running title: Diagnostic and prognostic value of BDNF Authors: Frederick K. Korley, MD, PhD Department of Emergency Medicine Johns Hopkins University School of Medicine, Baltimore, Maryland [email protected] Ramon Diaz-Arrastia, MD, PhD Center for Neuroscience and Regenerative Medicine Uniformed Services University of the Health Sciences 4301 Jones Bridge Road Bethesda, MD 20814 [email protected] Alan H. B. Wu Ph.D. Clinical Chemistry Laboratory San Francisco General Hospital 1001 Potrero Ave, San Francisco, CA 94110 [email protected]


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2 John K. Yue BA University of California San Francisco Department of Neurological Surgery 1001 Potrero Ave, Bldg. 1, Rm. 101 San Francisco, CA 94110 [email protected] Geoffrey T. Manley MD, PhD University of California, San Francisco Department of Neurological Surgery 505 Parnassus Ave. Rm. M779 San Francisco, CA 94143-0112 [email protected] Haris I. Sair M.D. Department of Radiology Johns Hopkins University School of Medicine Baltimore, Maryland [email protected] Jennifer Van Eyk Ph.D.* The Advanced Clinical Biosystems Research Institute


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3 The Heart Institute Department of Medicine Cedars Sinai Medical Center Los Angeles, California [email protected] Allen D. Everett M.D.* Department of Pediatrics Johns Hopkins University School of Medicine Baltimore, Maryland [email protected] and the TRACK-TBI Investigators including: David O. Okonkwo MD, PhD Department of Neurological Surgery University of Pittsburgh Medical Center 200 Lothrop St. Suite B-400 Pittsburgh, PA 15213 [email protected] Alex B. Valadka MD


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4 Seton Brain and Spine Institute 1400 N I-35, Ste 300 Austin, TX 78701 Tel: (512) 324-8300 [email protected] Wayne A. Gordon, Ph.D. Department of Rehabilitation Medicine Mount Sinai School of Medicine 3 East 101st Street, Room 118 Box 1240 New York, NY 10029 [email protected] Andrew I.R. Maas, MD, PhD Antwerp University Hospital Department of Neurosurgery UZA Wilrijkstraat 10 2650 Edegem Belgium [email protected] Pratik Mukherjee MD, PhD


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5 University of California, San Francisco Department of Radiology and Biomedical Imaging 185 Berry St. San Francisco, CA 94143 [email protected] Esther L. Yuh, MD, PhD University of California San Francisco Department of Radiology 185 Berry Street, Suite 350, San Francisco, CA, 94107 [email protected] Hester F. Lingsma PhD Erasmas Medical Center Department of Public Health Center for Medical Decision Making Dr. Molewaterplein 50 3015 GE Rotterdam [email protected] Ava M. Puccio, RN, PhD University of Pittsburgh Medical Center Department of Neurological Surgery 200 Lothrop St. Suite B-400


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6 Pittsburgh, PA 15213 [email protected] and David M. Schnyer, PhD Department of Psychology, University of Texas, Austin, TX [email protected]

Drs. Jennifer Van Eyk and Allen Everett contributed equally to this publication.

Address for correspondence: Frederick Korley M.D., Ph.D. Johns Hopkins University School of Medicine Davis Building, Suite 3220 5801 Smith Avenue Baltimore, Maryland 21209 Fax: 410-735-6440


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7 Telephone: 410-735-6400 Email: [email protected] Word Count: 3496

Disclosures: 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 NINDS, W81XWH-13-1-0441 from DOD USAMRAA, and Contract Number HHSN268201000032C from the 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 NIH.


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8 Abstract Introduction: Brain derived neurotrophic factor (BDNF) is important for neuronal survival and regeneration. We investigated the diagnostic and prognostic values of serum BDNF in TBI. Methods: We examined serum BDNF in two independent cohorts of TBI cases presenting to the emergency departments (ED) 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 (PCS) or a Glasgow Outcome Scale Extended (GOSE) score24 hours >24 hours

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