title: Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model.
abstract: 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.affiliation: Molecular Aging and Development Laboratory, Boston University School of Medicine, Boston, MA 02118, USA. lgold@bu.edu
authors.forename: Lee E
authors.initials: LE
authors.lastname: Goldstein
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Fisher
authors.forename: Chad A
authors.initials: CA
authors.lastname: Tagge
authors.forename: Xiao-Lei
authors.initials: XL
authors.lastname: Zhang
authors.forename: Libor
authors.initials: L
authors.lastname: Velisek
authors.forename: John A
authors.initials: JA
authors.lastname: Sullivan
authors.forename: Chirag
authors.initials: C
authors.lastname: Upreti
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Kracht
authors.forename: Maria
authors.initials: M
authors.lastname: Ericsson
authors.forename: Mark W
authors.initials: MW
authors.lastname: Wojnarowicz
authors.forename: Cezar J
authors.initials: CJ
authors.lastname: Goletiani
authors.forename: Giorgi M
authors.initials: GM
authors.lastname: Maglakelidze
authors.forename: Noel
authors.initials: N
authors.lastname: Casey
authors.forename: Juliet A
authors.initials: JA
authors.lastname: Moncaster
authors.forename: Olga
authors.initials: O
authors.lastname: Minaeva
authors.forename: Robert D
authors.initials: RD
authors.lastname: Moir
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Nowinski
authors.forename: Robert A
authors.initials: RA
authors.lastname: Stern
authors.forename: Robert C
authors.initials: RC
authors.lastname: Cantu
authors.forename: James
authors.initials: J
authors.lastname: Geiling
authors.forename: Jan K
authors.initials: JK
authors.lastname: Blusztajn
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Wolozin
authors.forename: Tsuneya
authors.initials: T
authors.lastname: Ikezu
authors.forename: Thor D
authors.initials: TD
authors.lastname: Stein
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Budson
authors.forename: Neil W
authors.initials: NW
authors.lastname: Kowall
authors.forename: David
authors.initials: D
authors.lastname: Chargin
authors.forename: Andre
authors.initials: A
authors.lastname: Sharon
authors.forename: Sudad
authors.initials: S
authors.lastname: Saman
authors.forename: Garth F
authors.initials: GF
authors.lastname: Hall
authors.forename: William C
authors.initials: WC
authors.lastname: Moss
authors.forename: Robin O
authors.initials: RO
authors.lastname: Cleveland
authors.forename: Rudolph E
authors.initials: RE
authors.lastname: Tanzi
authors.forename: Patric K
authors.initials: PK
authors.lastname: Stanton
authors.forename: Ann C
authors.initials: AC
authors.lastname: McKee
mesh_terms: D000054:Acceleration; D000293:Adolescent; D000328:Adult; D000818:Animals; D056352:Athletes; D001369:Axons / Q000473:pathology; D001522:Behavior, Animal; D001753:Blast Injuries / Q000150:complications* / Q000473:pathology* / Q000503:physiopathology; D001924:Brain Concussion / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D020208:Brain Injury, Chronic / Q000150:complications* / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D006257:Head / Q000473:pathology / Q000503:physiopathology; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D006801:Humans; D007427:Intracranial Pressure; D017774:Long-Term Potentiation; D008297:Male; D051379:Mice; D008875:Middle Aged; D008889:Military Personnel / Q000523:psychology*; D010766:Phosphorylation; D011180:Postmortem Changes; D009435:Synaptic Transmission; D014728:Veterans / Q000523:psychology*; D055815:Young Adult; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016875:tau Proteins