Citation

Di Pietro V, Ragusa M, Davies DJ, Su Z, Hazeldine J, Lazzarino G, Hill LJ, Crombie N, Foster M, Purrello M, Logan A, Belli A. J. Neurotrauma 2017; 34(11): 1948-1956.

Affiliation

Birmingham, United Kingdom of Great Britain and Northern Ireland ; A.Belli@bham.ac.uk.

Copyright

(Copyright © 2017, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2016.4857

PMID

28279125

Abstract

Traumatic brain injury (TBI) is the leading cause of death and disability under the age of 45 years 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. The expression of 754 miRNAs was analysed in serum of 5 mild TBI (mTBI) with extra-cranial injury (EC) patients, 5 severe TBI (sTBI) with EC patients and 5 healthy volunteers (HV) at 1 day and 15 days post injury, by using the TaqMan® Array Human MicroRNA A+B Cards. The aim was to find candidate biomarkers able to discriminate between mild and severe TBI. 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: T0-1h, T4-12h, T48-72h and 15 days from the injury. Analysis revealed 2 miRNAs (miR-425-5p, miR-502) were significantly downregulated (p<0.05) in mTBI at early time points and are ideal candidates for diagnosis of mTBI; two miRNAs (miR-21 and miR-335) were significantly upregulated (p<0.01) and are valid biomarkers for the diagnosis of sTBI. In addition, miR-425-5p is a strong predictive of 6-month outcome at T0-1h and T4-12h, whilst miR-21 is predictive of the outcome at T4-12h. The panel of selected miRNAs shows promise as biomarkers to discriminate mild from severe TBI. In addition the selected miRNAs represent new potential therapeutic targets.

Language: en

Keywords

ADULT BRAIN INJURY; BIOMARKERS; HEAD TRAUMA; NEURODEGENERATIVE DISORDERS; TRAUMATIC BRAIN INJURY