Systematic Review of the Diagnostic and Clinical Utility of Salivary microRNAs in Traumatic Brain Injury (TBI)

Abstract

Research in traumatic brain injury (TBI) is an urgent priority, as there are currently no TBI biomarkers to assess the severity of injury, to predict outcomes, and to monitor recovery. Small non-coding RNAs (sncRNAs) including microRNAs can be measured in saliva following TBI and have been investigated as potential diagnostic markers. The aim of this systematic review was to investigate the diagnostic or prognostic ability of microRNAs extracted from saliva in human subjects. PubMed, Embase, Scopus, PsycINFO and Web of Science were searched for studies that examined the association of saliva microRNAs in TBI. Original studies of any design involving diagnostic capacity of salivary microRNAs for TBI were selected for data extraction. Nine studies met inclusion criteria, with a heterogeneous population involving athletes and hospital patients, children and adults. The studies identified a total of 188 differentially expressed microRNAs, with 30 detected in multiple studies. MicroRNAs in multiple studies involved expression change bidirectionality. The study design and methods involved significant heterogeneity that precluded meta-analysis. Early data indicates salivary microRNAs may assist with TBI diagnosis. Further research with consistent methods and larger patient populations is required to evaluate the diagnostic and prognostic potential of saliva microRNAs.

Serum microRNAs associated with concussion in football players

“…A recent systematic review of salivary miRNA/TBI studies ( 31 ) is consistent with the results of our study. Eight of the nine reviewed studies contained exclusively mTBI subjects and seven of the nine involved acute mTBI.…”

“…Changes in plasma or serum miRNAs have been associated with a variety of diseases, including animal (19) and human severe (20)(21)(22)(23)(24)(25) and sport-related TBI (26)(27)(28)(29)(30). A recent systematic review of salivary miRNA in acute mTBI and persistent post-concussion syndrome revealed 14 miRNAs with consistent directional change after mTBI (31). One of the reviewed studies (32) developed a model combining symptoms and neurocognitive measures with miRNAs to aid with the diagnosis of mTBI, however, to date there are no biomarkers by themselves that identify or track acute mild TBI.…”

miR-21, miR-93, miR-191, miR-let-7b, and miR-499 Expression Level in Plasma and Cerebrospinal Fluid in Patients with Prolonged Disorders of Consciousness

“…Despite a large number of publications devoted to the miR study in patients with TBI and various neurodegenerative diseases, some fundamental issues remain unclear in the practical application of miR because its kinetics and the influence of biological factors and identifying of the specific miRs is an extremely difficult task [ 32 , 33 ]. New methods of miR investigation in patients’ saliva significantly increased the rate of obtaining biological material in a non-invasive way thus illustrating the high potential of this direction in the practical field [ 34 ]. Moreover, experimental techniques are being developed in the field of therapeutics of miR-based drugs.…”

Review on the Role of Salivary Biomarkers in the Diagnosis of Mild Traumatic Brain Injury and Post-Concussion Syndrome

“…Specific miRNAs in saliva are altered in individuals with mild TBI and PCS, suggesting that these miRNAs could be used as non-invasive biomarkers for these conditions. At least nine studies have shown 188 differentially expressed miRNAs, of which 30 were detected in most cases [ 50 ]. Di Pietro et al [ 51 ] investigated the role of salivary miRNAs on 1028 elite English rugby union players, by collecting samples during the preseason and standardized head injury assessments at in-game, post-game, and 36–48 h post-game periods.…”