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

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.

Screening the expression of several miRNAs from TaqMan Low Density Array in traumatic brain injury: miR‐219a‐5p regulates neuronal apoptosis by modulating CCNA2 and CACUL1

“…Moreover, most existing studies are either based on a limited number of patients, only focus on a few specific miRNAs or provide no prognostic results, which may partially explain some of the discrepancies observed (Redell et al ; Bhomia et al ; Yang et al ; Qin et al ). Recently, Di Pietro et al () screened miRNAs and validated that they were potential biomarkers for the diagnosis and prognosis of TBI using TaqMan Low Density Array (TLDA). Nevertheless, their study did not verify the function of these dysregulated miRNAs.…”

Bioinformatic analysis of brain-specific miRNAs for identification of candidate traumatic brain injury blood biomarkers

“…The experimental strategy employed in this investigation has several distinct advantages over those employed in the small number of large-scale miRNA biomarker discovery analyses performed in TBI to date. Most notably, PREPRINT 6 prior investigations have identified candidate miRNAs by high-throughput comparisons of circulating miRNAs between TBI patients and healthy controls [20,[24][25][26]. Thus, it is unclear whether the miRNAs identified in these studies exhibit elevation in blood which are specific to brain injury, or just trauma in general.…”

MicroRNAs as Potential Prognosticators of Neurological Outcome in Out-Of-Hospital Cardiac Arrest Patients

“…A recently published study described miRNAs that were able to discriminate mild from severe TBI at early time points (between 0 and 12 h, miR-425-5p and miR-502 are significantly downregulated in moderate TBI, while miR-21 and miR-335 are significantly upregulated in severe TBI) [42]. Furthermore, miR-425 and miR-21 strongly predicted neurological outcome at 6 months.…”