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

Steven Hicks, Jeremiah Johnson, Molly C. Carney, Harry Bramley, Robert Olympia, Andrea Loeffert, Neal Thomas

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)64-72
Number of pages9
JournalJournal of Neurotrauma
Volume35
Issue number1
DOIs
StatePublished - Jan 1 2018

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MicroRNAs
Saliva
Cerebrospinal Fluid
Pediatrics
Brain Concussion
Nonparametric Statistics
Traumatic Brain Injury
Biomarkers
Messenger RNA
Area Under Curve
Orthopedics
Exercise

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

Cite this

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abstract = "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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Overlapping MicroRNA Expression in Saliva and Cerebrospinal Fluid Accurately Identifies Pediatric Traumatic Brain Injury. / Hicks, Steven; Johnson, Jeremiah; Carney, Molly C.; Bramley, Harry; Olympia, Robert; Loeffert, Andrea; Thomas, Neal.

In: Journal of Neurotrauma, Vol. 35, No. 1, 01.01.2018, p. 64-72.

Research output: Contribution to journalArticle

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AU - Hicks, Steven

AU - Johnson, Jeremiah

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