Traumatic brain injury (TBI) is an important health concern for which effective treatment strategies remain elusive. Understanding the complex multi-cellular 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, microRNAs (miRNAs) in EVs have been shown to mediate neuroinflammation and neuronal injury.

To explore the role of EV associated miRNA in TBI, researchers from University of Nebraska Medical Center isolated EVs from the brains of injured mice and controls, purified RNA from brain EVs, and utilized LC Sciences’ miRNA sequencing service for profiling. Researchers 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 found to be primarily localized to neurons near the lesion site. Interestingly, adjacent to these miR-21-expressing neurons were activated microglia.

The concurrent increase of miR-21 in EVs with the elevation of miR-21 in neurons, suggest that miR-21 is secreted from neurons as potential EV cargo. Thus, this study revealed a new potential mechanism of cell–cell communication not previously described in TBI.

 

Sequencing of EV miRNAs after CCI

 

(A) Heat map and hierarchical clustering depicting all differentially expressed miRNAs (P < .05 by ANOVA). (B) Venn Diagram showing differentially expressed miRNAs in ipsilateral (IPSI) vs. sham left and contralateral (CONTRA) vs. sham right. (C) Log2 values for the contralateral hemisphere (CONTRA) are also shown.

 

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Reference

E. B. Harrison, C. G. Hochfelder, B. G. Lamberty, B. M. Meays, B. M. Morsey, M. L. Kelso, H. S. Fox, S. V. Yelamanchili (2016) Traumatic brain injury increases levels of miR-21 in extracellular vesicles: implications for Neuroinflammation FEBS Open Bio 6(8):835-46. [article]