MicroRNA sequencing of rat hippocampus and human biofluids identifies acute, chronic, focal and diffuse traumatic brain injuries

Harris A. Weisz, Deborah Kennedy, Steven Widen, Heidi Spratt, Stacy L. Sell, Christine Bailey, Melinda Moore, Douglas S. DeWitt, Donald S. Prough, Harvey Levin, Claudia Robertson, Helen L. Hellmich

Research output: Contribution to journalArticle

Abstract

High-throughput sequencing technologies could improve diagnosis and classification of TBI subgroups. Because recent studies showed that circulating microRNAs (miRNAs) may serve as noninvasive markers of TBI, we performed miRNA-seq to study TBI-induced changes in rat hippocampal miRNAs up to one year post-injury. We used miRNA PCR arrays to interrogate differences in serum miRNAs using two rat models of TBI (controlled cortical impact [CCI] and fluid percussion injury [FPI]). The translational potential of our results was evaluated by miRNA-seq analysis of human control and TBI (acute and chronic) serum samples. Bioinformatic analyses were performed using Ingenuity Pathway Analysis, miRDB, and Qlucore Omics Explorer. Rat miRNA profiles identified TBI across all acute and chronic intervals. Rat CCI and FPI displayed distinct serum miRNA profiles. Human miRNA profiles identified TBI across all acute and chronic time points and, at 24 hours, discriminated between focal and diffuse injuries. In both species, predicted gene targets of differentially expressed miRNAs are involved in neuroplasticity, immune function and neurorestoration. Chronically dysregulated miRNAs (miR-451a, miR-30d-5p, miR-145-5p, miR-204-5p) are linked to psychiatric and neurodegenerative disorders. These data suggest that circulating miRNAs in biofluids can be used as “molecular fingerprints” to identify acute, chronic, focal or diffuse TBI and potentially, presence of neurodegenerative sequelae.

Original languageEnglish (US)
Article number3341
JournalScientific reports
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'MicroRNA sequencing of rat hippocampus and human biofluids identifies acute, chronic, focal and diffuse traumatic brain injuries'. Together they form a unique fingerprint.

  • Cite this