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J Neurotrauma. 2017 Jun 1;34(11):1948-1956. doi: 10.1089/neu.2016.4857. Epub 2017 Apr 10.

MicroRNAs as Novel Biomarkers for the Diagnosis and Prognosis of Mild and Severe Traumatic Brain Injury.

Author information

1
1 Neurotrauma and Ophthalmology Research Group, Institute of Inflammation and Aging, University of Birmingham , Birmingham, United Kingdom .
2
2 National Institute for Health Research Surgical Reconstruction and Microbiology Research Center , Queen Elizabeth Hospital, Birmingham, United Kingdom .
3
3 Department of Biomedical Sciences and Biotechnology, University of Catania , Catania, Italy .
4
4 Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome , Rome, Italy .
5
5 West Midlands Air Ambulance Trust , West Midlands, United Kingdom .
6
6 Academic Department of Military Surgery and Trauma, Royal Center for Defense Medicine, Institute of Research and Development , Birmingham, United Kingdom .

Abstract

Traumatic brain injury (TBI) is the leading cause of death and disability in people younger than 45 in Western countries. Despite many studies, no reliable biomarkers have been found to assess TBI severity and predict recovery. MicroRNA (miRNA) profiling has become widely used to identify biomarkers and therapeutic targets. Through use of the TaqMan Array Human MicroRNA A+B Cards, the expression of 754 miRNAs was analyzed in serum of five mild TBI (mTBI) patients with extra-cranial injury (EC), five severe TBI (sTBI) patients with EC, and five healthy volunteers (HV) at 1 day and 15 days post-injury. The aim was to find candidate biomarkers able to discriminate between mTBI and sTBI. Following this, it was possible to select 10 miRNAs for further study in an enlarged validation cohort of 120 patients by using single TaqMan assays at the following time-points: T0-1 h, T4-12 h, T48-72 h, and 15 days from the injury. Analysis revealed two miRNAs (miR-425-5p and miR-502) that were significantly downregulated (p < 0.05) in mTBI at early time-points and are ideal candidates for diagnosis of mTBI, and two miRNAs (miR-21 and miR-335) that were significantly upregulated (p < 0.01) and are valid biomarkers for the diagnosis of sTBI. In addition, miR-425-5p was a strong predictor of 6-month outcome at T0-1 h and T4-12 h, while miR-21 was predictive of the outcome at T4-12 h. The panel of selected miRNAs shows promise as biomarkers to discriminate mTBI from sTBI. In addition, the selected miRNAs represent new potential therapeutic targets.

KEYWORDS:

biomarkers; concussion; diagnosis; microRNAs; prognosis; traumatic brain injury

PMID:
28279125
DOI:
10.1089/neu.2016.4857
[Indexed for MEDLINE]

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