RNA sequencing to map the molecular changes in brain-derived extracellular vesicles (EVs). (A) A schematic of various injury states designed for this study. The injury states for mice include different types (CCI, Blast), different intensities within each type (mild CCI, moderate CCI, low Blast, high Blast), different histories of injury (single, double), and various time-points post-injury (1 h, 1 day, 4 days, 14 days) for all the states including sham controls. The injury states for human include traumatic brain injury (TBI) patients with Abbreviated Injury Score 2–5 and healthy controls. (B) We compared signaling pathways that were activated in brain-derived EVs of TBI mice to those of TBI human patients. A total of 56 pathways were found to be significantly activated (p < 0.05) in TBI patients, and of these 56 pathways, 41 pathways were detected to be significant (p < 0.05) in TBI mouse models. SPRP, signaling pathways regulating pluripotency; GB, glycosaminoglycan biosynthesis. Color image is available online.