Traumatic brain injury increases levels of miR-21 in extracellular vesicles: Implications for neuroinflammation

Emily B. Harrison, Colleen G. Hochfelder, Benjamin G. Lamberty, Brittney M. Meays, Brenda M. Morsey, Matthew L. Kelso, Howard S Fox, Sowmya V Yelamanchili

Research output: Contribution to journalArticle

Abstract

Traumatic brain injury (TBI) is an important health concern and effective treatment strategies remain elusive. Understanding the complex multicellular response to TBI may provide new avenues for intervention. In the context of TBI, cell-cell communication is critical. One relatively unexplored form of cell-cell communication in TBI is extracellular vesicles (EVs). These membrane-bound vesicles can carry many different types of cargo between cells. Recently, miRNA in EVs have been shown to mediate neuroinflammation and neuronal injury. To explore the role of EV-associated miRNA in TBI, we isolated EVs from the brain of injured mice and controls, purified RNA from brain EVs, and performed miRNA sequencing. We found that the expression of miR-212 decreased, while miR-21, miR-146, miR-7a, and miR-7b were significantly increased with injury, with miR-21 showing the largest change between conditions. The expression of miR-21 in the brain was primarily localized to neurons near the lesion site. Interestingly, adjacent to these miR-21-expressing neurons were activated microglia. The concurrent increase in miR-21 in EVs with the elevation of miR-21 in neurons, suggests that miR-21 is secreted from neurons as potential EV cargo. Thus, this study reveals a new potential mechanism of cell-cell communication not previously described in TBI.

Original languageEnglish (US)
JournalFEBS Open Bio
Volume6
Issue number8
StateAccepted/In press - Aug 1 2016

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Keywords

  • Controlled cortical impact
  • Exosomes
  • MicroRNA
  • Microglia
  • Neuroinflammation
  • Secondary injury

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Harrison, E. B., Hochfelder, C. G., Lamberty, B. G., Meays, B. M., Morsey, B. M., Kelso, M. L., Fox, H. S., & Yelamanchili, S. V. (Accepted/In press). Traumatic brain injury increases levels of miR-21 in extracellular vesicles: Implications for neuroinflammation. FEBS Open Bio, 6(8).