Research Article
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Published Online: 1 January 2018

Overlapping MicroRNA Expression in Saliva and Cerebrospinal Fluid Accurately Identifies Pediatric Traumatic Brain Injury

Publication: Journal of Neurotrauma
Volume 35, Issue Number 1


To assess the accuracy and physiological relevance of circulating microRNA (miRNA) as a biomarker of pediatric concussion, we compared changes in salivary miRNA and cerebrospinal fluid (CSF) miRNA concentrations after childhood traumatic brain injury (TBI). A case-cohort design was used to compare longitudinal miRNA concentrations in CSF of seven children with severe TBI against three controls without TBI. The miRNAs “altered” in CSF were interrogated in saliva of 60 children with mild TBI and compared with 18 age- and sex-matched controls. The miRNAs with parallel changes (Wilcoxon rank sum test) in CSF and saliva were interrogated for predictive accuracy of TBI status using a multivariate regression technique. Spearman rank correlation identified relationships between miRNAs of interest and clinical features. Functional analysis with DIANA mirPath identified related mRNA pathways. There were 214 miRNAs detected in CSF, and 135 (63%) were also present in saliva. Six miRNAs had parallel changes in both CSF and saliva (miR-182-5p, miR-221-3p, mir-26b-5p, miR-320c, miR-29c-3p, miR-30e-5p). These miRNAs demonstrated an area under the curve of 0.852 for identifying mild TBI status. Three of the miRNAs exhibited longitudinal trends in CSF and/or saliva after TBI, and all three targeted mRNAs related to neuronal development. Concentrations of miR-320c were directly correlated with child and parent reports of attention difficulty. Salivary miRNA represents an easily measured, physiologically relevant, and accurate potential biomarker for TBI. Further studies assessing the influence of orthopedic injury and exercise on peripheral miRNA patterns are needed.

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Published In

cover image Journal of Neurotrauma
Journal of Neurotrauma
Volume 35Issue Number 1January 1, 2018
Pages: 64 - 72
PubMed: 28762893


Published in print: January 1, 2018
Published online: 1 January 2018
Published ahead of print: 27 October 2017
Published ahead of production: 1 August 2017


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Steven D. Hicks
Department of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania.
Jeremiah Johnson
Department of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania.
Molly C. Carney
Department of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania.
Harry Bramley
Department of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania.
Robert P. Olympia
Department of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania.
Department of Emergency Medicine, Penn State College of Medicine, Hershey, Pennsylvania.
Andrea C. Loeffert
Department of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania.
Neal J. Thomas
Department of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania.
Department of Public Health Sciences, Penn State College of Medicine, Hershey, Pennsylvania.


Address correspondence to:Steven D. Hicks, MD, PhDPenn State College of MedicineMail Code HS83500 University Drive, PO Box 850Hershey, PA 17033-0850E-mail: [email protected]

Author Disclosure Statement

Dr. Hicks is a co-inventor of preliminary patents for microRNA biomarkers in disorders of the central nervous system that is assigned to the SUNY Upstate and Penn State Research Foundations and licensed to Quadrant Biosciences (formerly Motion Intelligence). Dr. Hicks is also a consultant for Quadrant Biosciences. These conflicts of interest are currently managed by the Penn State College of Medicine. For the remaining authors, no competing financial interests exist.

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