低剂量沙林和环沙林暴露对海湾战争退伍军人白质完整性的影响。
Effects of low-level sarin and cyclosarin exposure on white matter integrity in Gulf War Veterans.
作者信息
Chao Linda L, Zhang Yu, Buckley Shannon
机构信息
Center for Imaging of Neurodegenerative Diseases, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, 114M, San Francisco, CA 94121, United States; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States; Department of Psychiatry, University of California San Francisco, San Francisco, CA, United States.
Center for Imaging of Neurodegenerative Diseases, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, 114M, San Francisco, CA 94121, United States; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States.
出版信息
Neurotoxicology. 2015 May;48:239-48. doi: 10.1016/j.neuro.2015.04.005. Epub 2015 Apr 27.
BACKGROUND
We previously found evidence of reduced gray and white matter volume in Gulf War (GW) veterans with predicted low-level exposure to sarin (GB) and cyclosarin (GF). Because loss of white matter tissue integrity has been linked to both gray and white matter atrophy, the current study sought to test the hypothesis that GW veterans with predicted GB/GF exposure have evidence of disrupted white matter microstructural integrity.
METHODS
Measures of fractional anisotropy and directional (i.e., axial and radial) diffusivity were assessed from the 4T diffusion tensor images (DTI) of 59 GW veterans with predicted GB/GF exposure and 59 "matched" unexposed GW veterans (mean age: 48 ± 7 years). The DTI data were analyzed using regions of interest (ROI) analyses that accounted for age, sex, total brain gray and white matter volume, trauma exposure, posttraumatic stress disorder, current major depression, and chronic multisymptom illness status.
RESULTS
There were no significant group differences in fractional anisotropy or radial diffusivity. However, there was increased axial diffusivity in GW veterans with predicted GB/GF exposure compared to matched, unexposed veterans throughout the brain, including the temporal stem, corona radiata, superior and inferior (hippocampal) cingulum, inferior and superior fronto-occipital fasciculus, internal and external capsule, and superficial cortical white matter blades. Post hoc analysis revealed significant correlations between higher fractional anisotropy and lower radial diffusivity with better neurobehavioral performance in unexposed GW veterans. In contrast, only increased axial diffusivity in posterior limb of the internal capsule was associated with better psychomotor function in GW veterans with predicted GB/GF exposure.
CONCLUSIONS
The finding that increased axial diffusivity in a region of the brain that contains descending corticospinal fibers was associated with better psychomotor function and the lack of significant neurobehavioral deficits in veterans with predicted GB/GF exposure hint at the possibility that the widespread increases in axial diffusivity that we observed in GW veterans with predicted GB/GF exposure relative to unexposed controls may reflect white matter reorganization after brain injury (i.e., exposure to GB/GF).
背景
我们之前发现，预测接触沙林（GB）和环沙林（GF）水平较低的海湾战争（GW）退伍军人存在灰质和白质体积减少的证据。由于白质组织完整性的丧失与灰质和白质萎缩均有关联，因此本研究旨在检验以下假设：预测接触GB/GF的GW退伍军人存在白质微结构完整性破坏的证据。
方法
从59名预测接触GB/GF的GW退伍军人和59名“匹配的”未接触GW退伍军人（平均年龄：48±7岁）的4T扩散张量图像（DTI）中评估各向异性分数和方向（即轴向和径向）扩散率。使用感兴趣区域（ROI）分析对DTI数据进行分析，该分析考虑了年龄、性别、全脑灰质和白质体积、创伤暴露、创伤后应激障碍、当前重度抑郁症以及慢性多症状疾病状态。
结果
各向异性分数或径向扩散率在两组间无显著差异。然而，与匹配的未接触退伍军人相比，预测接触GB/GF的GW退伍军人全脑的轴向扩散率增加，包括颞干、放射冠、上、下（海马）扣带、下和上额枕束、内囊和外囊以及浅表皮质白质板层。事后分析显示，在未接触GW退伍军人中，较高的各向异性分数和较低的径向扩散率与较好的神经行为表现之间存在显著相关性。相比之下，在预测接触GB/GF的GW退伍军人中，仅内囊后肢的轴向扩散率增加与较好的精神运动功能相关。
结论
在包含下行皮质脊髓纤维的脑区中，轴向扩散率增加与较好的精神运动功能相关，以及预测接触GB/GF的退伍军人缺乏显著神经行为缺陷，这表明我们在预测接触GB/GF的GW退伍军人中观察到的相对于未接触对照的轴向扩散率广泛增加，可能反映了脑损伤（即接触GB/GF）后的白质重组。
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