Effects of low-level sarin and cyclosarin exposure on hippocampal microstructure in Gulf War Veterans
Effects of low-level sarin and cyclosarin exposure on hippocampal microstructure in Gulf War Veterans
复制标题
DOI：
10.1016/j.ntt.2018.05.001
复制
发表时间：
2018-07-01
影响因子：
2.9
通讯作者：
Zhang, Yu
中科院分区：
文献类型：
--
作者：
Chao, Linda L.;Zhang, Yu
1991年3月初，海湾战争结束后不久，伊拉克哈米斯耶的一个弹药库被摧毁。后来，在1996年，该垃圾场被发现含有有机磷神经毒剂沙林和环沙林。我们以前报道过的证据表明，与未暴露的GW退伍军人相比，预测暴露于Khamisiyah羽的GW退伍军人的海马体积较小。为了调查这些宏观海马体积变化是否伴随着海马的微结构改变，目前的研究从170名GW退伍军人（平均年龄：53 +/- 7岁）获得了弥散张量成像（DTI），T1和T2加权图像，其中81人根据国防部（DOD）羽流建模预测暴露于Khamisiyah羽流。我们研究了分数各向异性（FA），平均扩散率（MD），和灰质（GM）密度从海马区的利益（ROI）。结果表明，即使在考虑了总海马GM密度（或海马体积）、年龄、性别、载脂蛋白e4基因型和潜在的混杂OP农药暴露后，海马MD仍能显著预测Khamisiyah暴露状态（模型p = 0.005，R-2 = 0.215，标准化系数β = 0.26，t = 2.85）。在整个研究样本中，海马MD也与非文字记忆学习表现呈负相关（p = 0.001）。海马FA或GM密度没有差异;然而，与未暴露的退伍军人相比，预测Khamisiyah暴露的退伍军人海马体积较小。由于MD是敏感的一般微观结构中断，导致细胞外空间增加，由于神经元死亡，炎症和神经胶质增生，和/或轴突损失或脱髓鞘，这些研究结果表明，低水平暴露于Khamisiyah羽具有有害的，持久的影响宏观和微观结构的海马。
In early March 1991, shortly after the end of the Gulf War (GW), a munitions dump was destroyed at Khamisiyah, Iraq. Later, in 1996, the dump was found to have contained the organophosphorus (OP) nerve agents sarin and cyclosarin. We previously reported evidence of smaller hippocampal volumes in GW veterans with predicted exposure to the Khamisiyah plume compared to unexposed GW veterans. To investigate whether these macroscopic hippocampal volume changes are accompanied by microstructural alterations in the hippocampus, the current study acquired diffusion-tensor imaging (DTI), T1-, and T2-weighted images from 170 GW veterans (mean age: 53 +/- 7 years), 81 of whom had predicted exposure to the Khamisiyah plume according to Department of Defense (DOD) plume modeling. We examined fractional anisotropy (FA), mean diffusivity (MD), and grey matter (GM) density from a hippocampal region of interest (ROI). Results indicate that, even after accounting for total hippocampal GM density (or hippocampal volume), age, sex, apolipoprotein e4 genotype, and potential confounding OP pesticide exposures, hippocampal MD significantly predicted Khamisiyah exposure status (model p = 0.005, R-2 = 0.215, standardized coefficient beta = 0.26, t = 2.85). Hippocampal MD was also inversely correlated with verbal memory learning performance in the entire study sample (p = 0.001). There were no differences in hippocampal FA or GM density; however, veterans with predicted Khamisiyah exposure had smaller hippocampal volumes compared to unexposed veterans. Because MD is sensitive to general microstructural disruptions that lead to increased extracellular spaces due to neuronal death, inflammation and gliosis, and/or to axonal loss or demyelination, these findings suggest that low-level exposure to the Khamisiyah plume has a detrimental, lasting effects on both macro- and micro-structure of the hippocampus.