TY  - JOUR
PY  - 2012//
TI  - Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model
JO  - Science translational medicine
A1  - Goldstein, Lee E.
A1  - Fisher, Andrew M.
A1  - Tagge, Chad A.
A1  - Zhang, Xiao-Lei
A1  - Velisek, Libor
A1  - Sullivan, John A.
A1  - Upreti, Chirag
A1  - Kracht, Jonathan M.
A1  - Ericsson, Maria
A1  - Wojnarowicz, Mark W.
A1  - Goletiani, Cezar J.
A1  - Maglakelidze, Giorgi M.
A1  - Casey, Noel
A1  - Moncaster, Juliet A.
A1  - Minaeva, Olga
A1  - Moir, Robert D.
A1  - Nowinski, Christopher J.
A1  - Stern, Robert A.
A1  - Cantu, Robert C.
A1  - Geiling, James
A1  - Blusztajn, Jan K.
A1  - Wolozin, Benjamin L.
A1  - Ikezu, Tsuneya
A1  - Stein, Thor D.
A1  - Budson, Andrew E.
A1  - Kowall, Neil W.
A1  - Chargin, David
A1  - Sharon, Andre
A1  - Saman, Sudad
A1  - Hall, Garth F.
A1  - Moss, William C.
A1  - Cleveland, Robin O.
A1  - Tanzi, Rudolph E.
A1  - Stanton, Patric K.
A1  - McKee, Ann C.
SP  - 134ra60
EP  - 134ra60
VL  - 4
IS  - 134
N2  - 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.<p />  <p>Language: en</p>
LA  - en
SN  - 1946-6234
UR  - http://dx.doi.org/10.1126/scitranslmed.3003716
ID  - ref1
ER  -