Research ArticleTraumatic Brain Injury

Chronic Traumatic Encephalopathy in Blast-Exposed Military Veterans and a Blast Neurotrauma Mouse Model

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Science Translational Medicine  16 May 2012:
Vol. 4, Issue 134, pp. 134ra60
DOI: 10.1126/scitranslmed.3003716

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Blast Brain: An Invisible Injury Revealed

Traumatic brain injury (TBI) is the “signature” injury of the conflicts in Afghanistan and Iraq and is associated with psychiatric symptoms and long-term cognitive disability. Recent estimates indicate that TBI may affect 20% of the 2.3 million U.S. servicemen and women deployed since 2001. Chronic traumatic encephalopathy (CTE), a tau protein–linked neurodegenerative disorder reported in athletes with multiple concussions, shares clinical features with TBI in military personnel exposed to explosive blast. However, the connection between TBI and CTE has not been explored in depth. In a new study, Goldstein et al. investigate this connection in the first case series of postmortem brains from U.S. military veterans with blast exposure and/or concussive injury. They report evidence for CTE neuropathology in the military veteran brains that is similar to that observed in the brains of young amateur American football players and a professional wrestler. The investigators developed a mouse model of blast neurotrauma that mimics typical blast conditions associated with military blast injury and discovered that blast-exposed mice also demonstrate CTE neuropathology, including tau protein hyperphosphorylation, myelinated axonopathy, microvascular damage, chronic neuroinflammation, and neurodegeneration. Surprisingly, blast-exposed mice developed CTE neuropathology within 2 weeks after exposure to a single blast. In addition, the neuropathology was accompanied by functional deficits, including slowed axonal conduction, reduced activity-dependent long-term synaptic plasticity, and impaired spatial learning and memory that persisted for 1 month after exposure to a single blast. The investigators then showed that blast winds with velocities of more than 330 miles/hour—greater than the most intense wind gust ever recorded on earth—induced oscillating head acceleration of sufficient intensity to injure the brain. The researchers then demonstrated that blast-induced learning and memory deficits in the mice were reduced by immobilizing the head during blast exposure. These findings provide a direct connection between blast TBI and CTE and indicate a primary role for blast wind–induced head acceleration in blast-related neurotrauma and its aftermath. This study also validates a new blast neurotrauma mouse model that will be useful for developing new diagnostics, therapeutics, and rehabilitative strategies for treating blast-related TBI and CTE.