Comprehensive assessment of shockwave intensity: Transcriptomic biomarker discovery for primary blast-induced mild traumatic brain injury using the mammalian hair follicle

Objective: Primary blast-induced mild traumatic brain injury (mTBI) is an injury experienced during modern warfare due to exposure to the pressure waves produced by the detonation of explosives. With virtually no apparent physical damage or symptoms presented, there is a need for more objective and accessible mTBI biomarkers posing minimal invasiveness risk. Methods: We measured the transcriptomic sensitivity of the hair follicles in relation to the severity of primary blast-derived TBI. An Advanced Blast Simulator system was used to expose male rats to single pulse shock waves (intensities ranging from 15 to 30 psi) in a head-only fashion. Gene differential expression (DE) and gene set (GS) analyses were conducted in the rat whisker hair follicles and the whole blood samples. Results: While shared cellular function, themes were found across the exposure groups, some gene sets under such themes were unique to the exposure conditions. Intensity-specific pathway enrichment patterns within shared GS themes were also identified. Furthermore, while exhibited shared pathways, the blood transcriptome showed substantially fewer enriched gene sets compared with the hair follicles across all exposure conditions. Conclusions: Accordingly, we demonstrate the potential of mammalian hair follicles serving as an additional source for biomarker discovery and for diagnosing mTBI with high accessibility.