Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model.
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 (...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2012
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| _version_ | 1826284581944295424 |
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| author | Goldstein, L Fisher, A Tagge, C Zhang, X Velisek, L Sullivan, J Upreti, C Kracht, J Ericsson, M Wojnarowicz, M Goletiani, C Maglakelidze, G Casey, N Moncaster, J Minaeva, O Moir, R Nowinski, C Stern, R Cantu, R Geiling, J Blusztajn, J Wolozin, B Ikezu, T Stein, T Budson, A |
| author_facet | Goldstein, L Fisher, A Tagge, C Zhang, X Velisek, L Sullivan, J Upreti, C Kracht, J Ericsson, M Wojnarowicz, M Goletiani, C Maglakelidze, G Casey, N Moncaster, J Minaeva, O Moir, R Nowinski, C Stern, R Cantu, R Geiling, J Blusztajn, J Wolozin, B Ikezu, T Stein, T Budson, A |
| author_sort | Goldstein, L |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T01:16:00Z |
| format | Journal article |
| id | oxford-uuid:8eb2077e-bb4b-4249-acc4-61696c7167e5 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:16:00Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:8eb2077e-bb4b-4249-acc4-61696c7167e52022-03-26T22:59:33ZChronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8eb2077e-bb4b-4249-acc4-61696c7167e5EnglishSymplectic Elements at Oxford2012Goldstein, LFisher, ATagge, CZhang, XVelisek, LSullivan, JUpreti, CKracht, JEricsson, MWojnarowicz, MGoletiani, CMaglakelidze, GCasey, NMoncaster, JMinaeva, OMoir, RNowinski, CStern, RCantu, RGeiling, JBlusztajn, JWolozin, BIkezu, TStein, TBudson, ABlast 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. |
| spellingShingle | Goldstein, L Fisher, A Tagge, C Zhang, X Velisek, L Sullivan, J Upreti, C Kracht, J Ericsson, M Wojnarowicz, M Goletiani, C Maglakelidze, G Casey, N Moncaster, J Minaeva, O Moir, R Nowinski, C Stern, R Cantu, R Geiling, J Blusztajn, J Wolozin, B Ikezu, T Stein, T Budson, A Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. |
| title | Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. |
| title_full | Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. |
| title_fullStr | Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. |
| title_full_unstemmed | Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. |
| title_short | Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. |
| title_sort | chronic traumatic encephalopathy in blast exposed military veterans and a blast neurotrauma mouse model |
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