AJND Copyright © Since 2012-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711, USA
Am J Neurodegener Dis 2012;1(1):88-98

Original Article
Select non-coding RNA in blood components provide novel clinically
accessible biological surrogates for improved identification of traumatic
brain injury in OEF/OIF Veterans

Giulio M Pasinetti, Lap Ho, Christopher Dooley, Bhavna Abbi, Gudrun Lange

Department of Neurology, Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA; GRECC, James J.
Peters Veterans Affairs Medical Center, Bronx NY 10468, USA; War-Related Illness & Injury Study Center, U.S.
Department of Veterans Affairs, 385 Tremont Avenue, East Orange, NJ 07018, USA; Department of Physical Medicine
and Rehabilitation, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA.

Received April 18, 2012; accepted April 23, 2012; Epub April 24, 2012; published May 30, 2012

Abstract: This study was designed to identify clinically accessible molecular biomarkers of mild traumatic brain injury
(mTBI) that could be used to help identify returning Operation Iraqi Freedom (OIF) and Operation Enduring Freedom
(OEF) Veterans who are suffering from the effects of mTBI. While analyzing the expression profile of small non-coding
RNAs in peripheral blood mononuclear cells (PBMCs) from an OEF/OIF veteran study cohort using a high throughput
Array chip platform, we identified 18 candidate small non-coding RNA biomarkers that are differentially regulated in
PBMCs of mTBI compared to non-TBI control cases. Independent quantitative real-time polymerase chain reaction
assays confirmed that 13 of these candidate small RNA biomarker species are, indeed, significantly down-regulated in
PBMCs of mTBI compared to non-TBI control veteran cases. Based on unsupervised clustering analysis, we identified
a 3-biomarker panel which was most able to distinguish mTBI from non-TBI control veteran cases with high accuracy,
selectivity and specificity.  The majority of mTBI cases in our biomarker study were co-morbid with Post-Traumatic
Stress Disorder (PTSD), and thus our non-TBI control cases were selected to match PTSD diagnoses. Therefore, our
identified panel of 3 small RNA biomarkers likely represents a biological index selective for mTBI. Outcomes from our
studies suggest that additional applications of the clinically accessible small non-coding RNA biomarkers to current
diagnostic criteria may lead to improved mTBI detection and more sensitive outcome measures for clinical trials.
Future studies exploring the physiological relevance of mTBI biomarkers will also provide a better understanding of the
biological mechanisms underlying mTBI and insights into novel therapeutic targets for mTBI. (AJND1104005)

Keywords: Mild traumatic brain injury (mTBI), biomarkers, microRNA (miRNA), post-traumatic stress disorder (PTSD)

Address all correspondence to:
Giulio Maria Pasinetti, MD, PhD
Department of Neurology
Mount Sinai School of Medicine
1468 Madison Avenue
Annenberg Building, Room 20-02
New York, NY 10029, USA
Phone:  212-241-7938 or 212-241-5563  
Fax:  212-876-9042
Email: Giulio.Pasinetti@mssm.edu