US Department of Defense
Advancing Blast Injury Research to Protect and Heal Those Who Serve

Transcriptomics as Biomarkers for Traumatic Brain Injury

Mild traumatic brain injury (mTBI) often results from the initial shock wave transmission after exposure to blast events. The subtle cellular, or subcellular, damages after blast exposure may be compounded by repeated exposures to trauma-inducing blast events. Without proper treatment, these subtle changes may escalate into considerably more severe chronic brain disorders. To address the need for a reliable and minimally invasive diagnostic technique for brain injury, researchers at the Royal Military College of Canada, University of New Brunswick and Canadian Rivers Institute, Defense Research and Development Canada, and the University of Florida, have investigated potential objective and accessible mTBI biomarkers. Using a rat model of brain injury, the researchers examined transcriptomic changes in hair follicles, combining differential gene expression comparisons with analyses of adapted comprehensive gene set analysis that focus on biological process, molecular function, or functional gene sets.

The researchers utilized an advanced blast simulator to deliver head-only exposure to rats at intensities of 15, 20, 25, and 30 pounds per square inch (psi). Rat whisker hair follicles and whole blood samples were collected one day after exposure and stored for later analysis using gene set analysis, quantitative RT-PCR, and by RNA micro-array based gene expression analysis. Gene expression profiles were determined and compared across blast intensities, as well as between hair follicles and whole blood samples. Even at the lowest psi shock wave exposure, significant changes in follicular gene expression occurred, with some genes being upregulated and others showing decreased expression. The greater the intensity of the blast exposure, the greater the number of genes were impacted, and typically the greater the magnitude of the change. Additionally, there were notable differences in the gene expression change profiles between blood samples and hair follicle tissues, suggesting that hair follicles may be an additional mTBI gene marker.

Blast-exposure resulted in transcriptomic responses in multiple biological or cellular themes - including cellular proliferation, ionic balance, blood brain integrity, tight junction disruption and others. Accordingly, mammalian hair follicles may represent an ideal biomarker for identifying blast-induced mTBI. The results of this study also suggest the likelihood of expanding the use of this diagnostic technique to other types of mechanically-induced injury.

This work was funded by the Defence Research and Development Canada (DRDC) Technology Investment Fund (TIF).


1. Zhang J, Knight R, Wang Y, Sawyer TW, Martyniuk CJ, and Langlois VS. (2017). Comprehensive assessment of shockwave intensity: transcriptomic biomarker discovery for primary blast-induced mild traumatic brain injury using the mammalian hair follicle. Brain Injury. DOI:10.1080/02699052.2017.1342000. ePub ahead of print.

Last modified: 03-Jan-2018