A Review of MicroRNA Biomarkers in Traumatic Brain Injury

Abstract

There is growing public concern surrounding traumatic brain injury (TBI). TBI can cause significant morbidity, and the long-term sequelae are poorly understood. TBI diagnosis and management rely on patient-reported symptoms and subjective clinical assessment. There are no biologic tools to detect mild TBI or to track brain recovery. Emerging evidence suggests that microRNAs (miRNAs) may provide information about the injured brain. These tiny epigenetic molecules are expressed throughout the body. However, they are particularly important in neurons, can cross the blood-brain barrier, and are securely transported from cell to cell, where they regulate gene expression. miRNA levels may identify patients with TBI and predict symptom duration. This review synthesizes miRNA findings from 14 human studies. We distill more than 291 miRNAs to 17 biomarker candidates that overlap across multiple studies and multiple biofluids. The goal of this review is to establish a collective understanding of miRNA biology in TBI and identify clinical priorities for future investigations of this promising biomarker.

Keywords: Concussion; biomarkers; diagnosis; miRNA; prognosis; traumatic brain injury; treatment.

Figure 1.

(a) Acute injury response of miRNAs: across 3 biofluids (cerebrospinal fluid, saliva, and blood) in the acute period (<96 hours post injury); (b) secondary injury response of miRNAs: across 3 biofluids (cerebrospinal fluid, saliva, and blood) in the subacute or chronic period (>5 days post injury). CSF, cerebrospinal fluid; miRNA, microRNA; TBI, traumatic brain injury. Arrows denote the general direction of change for each miRNA, along with the study in which it was detected (the superscript number corresponds to the reference). Gray boxes denote the time-points or biofluids without existing miRNA TBI studies.