Repeated mild blast exposure in young adult rats results in dynamic and persistent microstructural changes in the brain.
Repeated mild blast exposure in young adult rats results in dynamic and persistent microstructural changes in the brain.
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DOI：
10.1016/j.nicl.2018.01.007
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Agoston DV
中科院分区：
文献类型：
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作者：
Badea A;Kamnaksh A;Anderson RJ;Calabrese E;Long JB;Agoston DV
轻度创伤性脑损伤(MTBI)的病史，特别是反复mTBI(RmTBI)，已被认为是迟发性神经退行性疾病的危险因素。早期症状的轻微和短暂性质往往阻碍年轻人的诊断，他们受到MTBI的影响不成比例。一部分受影响的人群将招致长期的行为和认知后果，但潜在的致病机制目前尚不清楚。弥散张量成像(DTI)对脑外伤后脑组织结构改变(包括脑白质损伤)提供了敏感和定量的评估，并可用于预测长期预后。我们在冲击性rmTBI动物模型中使用弥散张量成像来量化冲击伤后7天和90 天的结构变化，以及它们在这两个时间点之间的演变。年轻成年雄性大鼠(伤时~p65)暴露于反复轻度冲击波超压，或麻醉为假手术，用高场(7 T)磁共振成像。我们发现，从7到90 天，损伤和假手术组大鼠的全脑体积也有类似的增加。然而，我们检测到爆炸暴露的动物在伤后7 天局部体积增加，主要是与入射冲击波同侧。受累区域包括额联合灰质、扣带回和运动皮质、丘脑、黑质和中缝核团(正中和背侧)，以及内囊和大脑脚的白质。相反，我们在损伤后90 天测量了这些区域和其他区域，包括海马体和小脑的体积减少。DTI还检测到损伤后短暂和持久的微结构变化，其中一些变化显示出与爆炸冲击相关的同侧和对侧的明显差异。早期的分数各向异性(FA)变化很轻微，在90 天时，大脑和小脑脚下部以及小脑白质变得更加明显。损伤后7 的径向弥散系数(RD)和轴向弥散系数(主本征值或E_1)的普遍增加在90 天后基本消退，尽管RD在检测白质改变方面比E_1更敏感。灰质和白质中的E1效应，与表观弥散增加平行，可能更多地表明水平衡失调，而不是病理结构变化。重要的是，我们发现了rmbTBI后不同发展轨迹的证据，如显著的损伤x年龄交互作用对体积的指示。我们的研究结果表明，rmbTBI启动了动态的病理生物学过程，可能会对晚期神经发育的进程产生负面影响，并对长期认知和行为结果产生不利影响。暴露在轻度冲击波下的年轻成年大鼠表现出持久的脑微结构变化。DTI测量的时间变化反映了mTBI病理的演变。局部体积变化捕捉到了显著的损伤 × 年龄交互作用。DTI测量不同的白质和灰质的损伤效应。显著的交互作用表明了一种改变的发展轨迹。
A history of mild traumatic brain injury (mTBI), particularly repeated mTBI (rmTBI), has been identified as a risk factor for late-onset neurodegenerative conditions. The mild and transient nature of early symptoms often impedes diagnosis in young adults who are disproportionately affected by mTBIs. A proportion of the affected population will incur long-term behavioral and cognitive consequences but the underlying pathomechanism is currently unknown. Diffusion tensor imaging (DTI) provides sensitive and quantitative assessment of TBI-induced structural changes, including white matter injury, and may be used to predict long-term outcome. We used DTI in an animal model of blast rmTBI (rmbTBI) to quantify blast-induced structural changes at 7 and 90 days post-injury, and their evolution between the two time points. Young adult male rats (~P65 at injury) were exposed to repeated mild blast overpressure, or anesthetized as shams, and their fixed brains were imaged using high-field (7 T) MRI. We found that whole brain volumes similarly increased in injured and sham rats from 7 to 90 days. However, we detected localized volume increases in blast-exposed animals 7 days post-injury, mainly ipsilateral to incident blast waves. Affected regions included gray matter of the frontal association, cingulate, and motor cortex, thalamus, substantia nigra, and raphe nuclei (median and dorsal), as well as white matter of the internal capsule and cerebral peduncle. Conversely, we measured volume reductions in these and other regions, including the hippocampus and cerebellum, at 90 days post-injury. DTI also detected both transient and persistent microstructural changes following injury, with some changes showing distinct ipsilateral versus contralateral side differences relative to blast impact. Early changes in fractional anisotropy (FA) were subtle, becoming more prominent at 90 days in the cerebral and inferior cerebellar peduncles, and cerebellar white matter. Widespread increases in radial diffusivity (RD) and axial diffusivity (primary eigenvalue or E1) at 7 days post-injury largely subsided by 90 days, although RD was more sensitive than E1 at detecting white matter changes. E1 effects in gray and white matter, which paralleled increases in apparent diffusion, were likely more indicative of dysregulated water homeostasis than pathologic structural changes. Importantly, we found evidence for a different developmental trajectory following rmbTBI, as indicated by significant injury x age interactions on volume. Our findings demonstrate that rmbTBI initiates dynamic pathobiological processes that may negatively alter the course of late-stage neurodevelopment and adversely affect long-term cognitive and behavioral outcomes. Young adult rats exposed to mild blast show lasting microstructural brain changes. The evolution of mTBI pathology was reflected by temporal changes in DTI measures. Regional volume changes captured significant injury × age interactions. DTI measures differentially captured injury effects in white and gray matter. Significant interaction effects suggest an altered developmental trajectory.
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影响因子：
5.7
作者：
Badea, Alexandra;Gewalt, Sally;Avants, Brian B.;Cook, James J.;Johnson, G. Allan
通讯作者：
Johnson, G. Allan
影响因子：
5.7
作者：
Giorgio, Antonio;Santelli, Luca;Tomassini, Valentina;Bosnell, Rose;Smith, Steve;De Stefano, Nicola;Johansen-Berg, Heidi
通讯作者：
Johansen-Berg, Heidi
影响因子：
5.7
作者：
Calabrese E;Badea A;Watson C;Johnson GA
通讯作者：
Johnson GA
影响因子：
4.2
作者：
Bazarian, Jeffrey J.;Zhong, Jianhui;Peterson, Derick
通讯作者：
Peterson, Derick
DOI：
10.1038/jcbfm.2009.203
发表时间：
2010-02
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
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作者：
通讯作者：
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