Hippocampal neurogenesis-related transcriptome signatures are modulated by force-dependent manner in animal model of traumatic brain injury. Transcriptome analysis of QCM-TBI

Traumatic brain injury (TBI) causes neurodegenerative diseases but the precise mechanism is not fully understood. Herein, we present a novel closed-head injury model, named Quantitatively Controlled and Measured-Traumatic Brain Injury (QCM-TBI), that accurately controls and measures the actual amount of impact delivered to the brain. The QCM-TBI system is designed with a unique gravity-compensating animal support system that replicates natural head motion in human TBI. Using QCM-TBI in conjunction with a multimodal sensor technique, we measured instantaneous force over the time of collision, while compensating distortion led by extreme acceleration of the force sensor. To validate QCM-TBI animal model, we conducted transcriptome analysis using QCM-TBI animal model and compared with CTE human transcriptome data. We found that synapse-and neurogenesis-related genes were markedly decreased in both QCM-TBI animal model and human CTE. Especially, doublecortin (Dcx), an essential marker of neurogenesis, was force-dependently dysregulated in QCM-TBI model and down-regulated in CTE. Moreover, the QCM-TBI animal model showed a correlation between the degree of impact and neuropathological and behavioral changes, such as increased phosphorylated Tau (p-Tau) and amyloid precursor protein (APP) levels and reduced neurofilament intensity and length, similar to the changes found in human TBI. Together, this QCM-TBI model is pivotal for studying concussion and the pathological outcomes.