Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model.
Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model.
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DOI：
10.1126/scitranslmed.3003716
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发表时间：
2012-05-16
影响因子：
17.1
通讯作者：
McKee AC
中科院分区：
文献类型：
--
作者：
Goldstein LE;Fisher AM;Tagge CA;Zhang XL;Velisek L;Sullivan JA;Upreti C;Kracht JM;Ericsson M;Wojnarowicz MW;Goletiani CJ;Maglakelidze GM;Casey N;Moncaster JA;Minaeva O;Moir RD;Nowinski CJ;Stern RA;Cantu RC;Geiling J;Blusztajn JK;Wolozin BL;Ikezu T;Stein TD;Budson AE;Kowall NW;Chargin D;Sharon A;Saman S;Hall GF;Moss WC;Cleveland RO;Tanzi RE;Stanton PK;McKee AC
爆炸暴露与创伤性脑损伤（TBI）、神经精神症状和长期认知障碍有关。我们研究了一系列暴露于爆炸和/或震荡损伤的美国退伍军人的死后大脑。我们发现了慢性创伤性脑病（CTE）的证据，这是一种与tau蛋白相关的神经退行性疾病，与年轻的业余美式足球运动员和有脑震荡损伤史的职业摔跤手观察到的CTE神经病理学相似。我们开发了一种冲击波神经创伤小鼠模型，该模型在暴露于单一冲击波2周后再现了野生型C57 BL/6小鼠中CTE相关的神经病理学。在没有肉眼可见的组织损伤或出血的情况下，暴露于爆炸物的小鼠表现出磷酸化tau蛋白病、有髓鞘轴突病、微血管病、慢性神经炎症和神经变性。爆炸暴露诱导持续性的海马依赖性学习和记忆缺陷，持续至少1个月，并与受损的轴突传导和有缺陷的活动依赖性长时程增强的突触传递。脑内压力记录表明，冲击波穿过小鼠大脑的变化最小，没有胸部的贡献。运动学分析显示，爆炸引起的头部振荡加速度足以造成脑损伤。爆炸暴露期间头部固定可防止爆炸引起的学习和记忆缺陷。爆炸风对头部损伤性加速度的作用可能是导致爆炸相关TBI和CTE的主要损伤机制。这些结果确定了导致爆炸暴露的退伍军人和头部受伤的运动员CTE的常见致病因素，并提供了将爆炸暴露与神经生理功能，学习和记忆的持续损伤联系起来的机制证据。
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.
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影响因子：
13.6
作者：
Formby, SA;Wharton, RK
通讯作者：
Wharton, RK
影响因子：
4.5
作者：
Elsayed, NM
通讯作者：
Elsayed, NM
DOI：
10.1037/h0077579
发表时间：
1979-01-01
期刊：
JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY
影响因子：
--
作者：
BARNES, CA
通讯作者：
BARNES, CA
DOI：
10.1249/mss.0b013e3181dd9156
发表时间：
2010-11-01
期刊：
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
影响因子：
--
作者：
Broglio, Steven P.;Schnebel, Brock;Zimmerman, Jerrad
通讯作者：
Zimmerman, Jerrad
影响因子：
3.5
作者：
Cloots, R. J. H.;van Dommelen, J. A. W.;Geers, M. G. D.
通讯作者：
Geers, M. G. D.