Modeling the Long-Term Consequences of Repeated Blast-Induced Mild Traumatic Brain Injuries

Repeated mild traumatic brain injury (rmTBI) caused by playing collision sports or by exposure to blasts during military operations can lead to late onset, chronic diseases such as chronic traumatic encephalopathy (CTE), a progressive neurodegenerative condition that manifests in increasingly severe neuropsychiatric abnormalities years after the last injury. Currently, because of the heterogeneity of the clinical presentation, confirmation of a CTE diagnosis requires post-mortem examination of the brain. The hallmarks of CTE are abnormal accumulation of phosphorylated tau protein, TDP-43 immunoreactive neuronal cytoplasmic inclusions, and astroglial abnormalities, but the pathomechanism leading to these terminal findings remains unknown. Animal modeling can play an important role in the identification of CTE pathomechanisms, the development of early stage diagnostic and prognostic biomarkers, and pharmacological interventions. Modeling the long-term consequences of blast rmTBI in animals is especially challenging because of the complexities of blast physics and animal-to-human scaling issues. This review summarizes current knowledge about the pathobiologies of CTE and rmbTBI and discusses problems as well as potential solutions related to high-fidelity modeling of rmbTBI and determining its long-term consequences.