Peripheral microRNA alteration and pathway signaling after mild traumatic brain injury

Discovering novel diagnostic biomarkers and signatures for traumatic brain injury (TBI) represents a major challenge in the brain trauma research. Detailed analysis of post-concussive molecular pathways based on experimental data could provide a new insight into the pathophysiological sequelae and mapping of recovery mechanisms involved in TBI. MicroRNAs (miRNAs) detectable in peripheral body fluids after TBI are promising carriers of this missing knowledge. In order to define the signature of peripheral miRNAs signaling associated with mild TBI (mTBI), we performed a comprehensive meta-analysis of miRNA profiles in mTBI patients using multiple curated pathway databases. Using a bioinformatic pipeline with integrated data analysis we identified a set of genes that are connected to deregulated circulating miRNAs following the mTBI. Identified genes belong to specific pathways of MAPK, TGF-beta, WNT, TLR2/4, PI3K/AKT, insulin, and growth factor signaling. Since the enriched pathways markedly overlap among the various biological fluids, signaling associated with mTBI that is concomitantly reflected in serum, plasma and saliva is robust and unique. Furthermore, we identified a network of 33 validated interacting proteins and their regulatory miRNAs that link the post-mTBI signaling in peripheral fluids with neurodegenerationassociated interaction pathways. Presented data provide a comprehensive insight into molecular events following mTBI, and the top predicted genes represent a group of novel candidate targets to be validated in connection with mTBI.