Plasma Exosome-derived MicroRNAs as Novel Biomarkers of Traumatic Brain Injury in Rats.

ABSTRACT

Traumatic brain injury (TBI) is a widespread central nervous system (CNS) condition and a leading cause of death, disability, and long-term disability including seizures and emotional and behavioral issues. To date, applicable diagnostic biomarkers have not been elucidated. MicroRNAs (miRNAs) are enriched and stable in exosomes in plasma. Therefore, we speculated that miRNAs in plasma exosomes might serve as novel biomarkers for TBI diagnosis and are also involved in the pathogenesis of TBI. In this study, we first isolated exosomes from peripheral blood plasma in rats with TBI and then investigated the alterations in miRNA expression in exosomes by high-throughput RNA sequencing. As a result, we identified 50 significantly differentially expressed miRNAs, including 31 upregulated and 19 downregulated miRNAs. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the most highly correlated pathways that were identified were the MAPK signaling pathway, regulation of actin cytoskeleton, Rap1 signaling pathway and Ras signaling pathway. This study provides novel perspectives on miRNAs in peripheral blood plasma exosomes, which not only could be used as biomarkers of TBI diagnosis but could also be manipulated as therapeutic targets of TBI.