Lifelong behavioral and neuropathological consequences of repetitive mild traumatic brain injury.
Lifelong behavioral and neuropathological consequences of repetitive mild traumatic brain injury.
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重复性轻度创伤性脑损伤的终生行为和神经病理学后果。
DOI：
10.1002/acn3.510
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发表时间：
2018-01
影响因子：
5.3
通讯作者：
Crawford F
中科院分区：
文献类型：
--
作者：
Mouzon BC;Bachmeier C;Ojo JO;Acker CM;Ferguson S;Paris D;Ait-Ghezala G;Crynen G;Davies P;Mullan M;Stewart W;Crawford F
暴露于反复脑震荡或轻度创伤性脑损伤（mTBI）与长期神经退行性变化的风险增加有关，特别是慢性创伤性脑病（CTE）。到目前为止，临床前研究主要集中在mTBI的直接后果，没有关于这些模型中mTBI终身后果的文献。这项研究首次报道了重复性mTBI的终身神经行为和组织学后果，为晚期生存的演变和持续病理学提供了独特的见解。将雄性C57 BL/6 J小鼠（2-3月龄）暴露于单次或重复的轻度TBI或假手术。此后，在最后一次损伤后24个月，对动物进行监测和评估，以测量运动协调、学习缺陷、认知功能和焦虑样行为，然后实施安乐死，并准备大脑进行详细的神经病理学和蛋白质生化研究。在24个月时，与假手术动物相比，暴露于r-mTBI的存活动物显示出学习和工作记忆障碍的明显证据，缺乏空间记忆和前庭-运动前庭功能障碍。与这些晚期行为缺陷相关的证据是皮质下白色物质束中持续的轴突变性和神经炎症。值得注意的是，在单次mTBI后也观察到这些变化，尽管程度低于重复mTBI。在这种情况下，我们目前的数据首次表明，轻度TBI不是急性、有时间限制的事件，而是会引发终生的退行性过程。因此，这些数据表明，成功的治疗策略应考虑急性和慢性mTBI的性质。
Exposure to repetitive concussion, or mild traumatic brain injury (mTBI), has been linked with increased risk of long‐term neurodegenerative changes, specifically chronic traumatic encephalopathy (CTE). To date, preclinical studies largely have focused on the immediate aftermath of mTBI, with no literature on the lifelong consequences of mTBI in these models. This study provides the first account of lifelong neurobehavioral and histological consequences of repetitive mTBI providing unique insight into the constellation of evolving and ongoing pathologies with late survival. Male C57BL/6J mice (aged 2–3 months) were exposed to either single or repetitive mild TBI or sham procedure. Thereafter, animals were monitored and assessed at 24 months post last injury for measures of motor coordination, learning deficits, cognitive function, and anxiety‐like behavior prior to euthanasia and preparation of the brains for detailed neuropathological and protein biochemical studies. At 24 months survival animals exposed to r‐mTBI showed clear evidence of learning and working memory impairment with a lack of spatial memory and vestibule‐motor vestibulomotor deficits compared to sham animals. Associated with these late behavioral deficits there was evidence of ongoing axonal degeneration and neuroinflammation in subcortical white matter tracts. Notably, these changes were also observed after a single mTBI, albeit to a lesser degree than repetitive mTBI. In this context, our current data demonstrate, for the first time, that rather than an acute, time limited event, mild TBI can precipitate a lifelong degenerative process. These data therefore suggest that successful treatment strategies should consider both the acute and chronic nature of mTBI.
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影响因子：
12.7
作者：
Ling H;Morris HR;Neal JW;Lees AJ;Hardy J;Holton JL;Revesz T;Williams DD
通讯作者：
Williams DD
DOI：
10.1097/nen.0b013e3181ee7d85
发表时间：
2010-09
影响因子：
3.2
作者：
McKee AC;Gavett BE;Stern RA;Nowinski CJ;Cantu RC;Kowall NW;Perl DP;Hedley-Whyte ET;Price B;Sullivan C;Morin P;Lee HS;Kubilus CA;Daneshvar DH;Wulff M;Budson AE
通讯作者：
Budson AE
影响因子：
12.7
作者：
Johnson VE;Stewart W;Weber MT;Cullen DK;Siman R;Smith DH
通讯作者：
Smith DH
影响因子：
4.8
作者：
Longhi, L;Saatman, KE;McIntosh, TK
通讯作者：
McIntosh, TK
影响因子：
4.2
作者：
Ferguson, Scott;Mouzon, Benoit;Crawford, Fiona
通讯作者：
Crawford, Fiona