Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model.

Journal article

Blast exposure is associated with traumatic brain injury (TBI), neuropsychiatric symptoms, and long-term cognitive disability. We examined a case series of postmortem brains from U.S. military veterans exposed to blast and/or concussive injury. We found evidence of chronic traumatic encephalopathy (CTE), a tau protein-linked neurodegenerative disease, that was similar to the CTE neuropathology observed in young amateur American football players and a professional wrestler with histories of concussive injuries. We developed a blast neurotrauma mouse model that recapitulated CTE-linked neuropathology in wild-type C57BL/6 mice 2 weeks after exposure to a single blast. Blast-exposed mice demonstrated phosphorylated tauopathy, myelinated axonopathy, microvasculopathy, chronic neuroinflammation, and neurodegeneration in the absence of macroscopic tissue damage or hemorrhage. Blast exposure induced persistent hippocampal-dependent learning and memory deficits that persisted for at least 1 month and correlated with impaired axonal conduction and defective activity-dependent long-term potentiation of synaptic transmission. Intracerebral pressure recordings demonstrated that shock waves traversed the mouse brain with minimal change and without thoracic contributions. Kinematic analysis revealed blast-induced head oscillation at accelerations sufficient to cause brain injury. Head immobilization during blast exposure prevented blast-induced learning and memory deficits. The contribution of blast wind to injurious head acceleration may be a primary injury mechanism leading to blast-related TBI and CTE. These results identify common pathogenic determinants leading to CTE in blast-exposed military veterans and head-injured athletes and additionally provide mechanistic evidence linking blast exposure to persistent impairments in neurophysiological function, learning, and memory.

Authors: Goldstein, L; Fisher, A; Tagge, C; Zhang, X; Velisek, L

• Publication status: Published
• Journal: Science translational medicine
• Volume: 4
• Issue: 134
• Pages: 134ra60
• Publication date: 2012-05-01
• DOI: 10.1126/scitranslmed.3003716
• EISSN: 1946-6242
• ISSN: 1946-6234
• Language: English
• Keywords: Male; tau Proteins; Brain Concussion; Head; Phosphorylation; Behavior, Animal; Humans; Long-Term Potentiation; Middle Aged; Synaptic Transmission; Veterans; Animals; Mice; Military Personnel; Intracranial Pressure; Postmortem Changes; Athletes; Adult; Young Adult; Brain Injury, Chronic; Blast Injuries; Disease Models, Animal; Adolescent; Acceleration; Axons; Hippocampus