Wu Xin, Shetty Ashok K, Reddy Doodipala Samba
Departments of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, TX, USA.
Departments of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, TX, USA; Institute for Regenerative Medicine, Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University, College Station, TX, USA.
Life Sci. 2021 Nov 15;285:119971. doi: 10.1016/j.lfs.2021.119971. Epub 2021 Sep 21.
Gulf War Illness (GWI) is a multi-symptom disease with debilitating cognitive and emotional impairments in veterans. GWI, like epilepsy, is caused by chemical neurotoxicity and manifests from disturbances in neuronal excitability. However, the mechanisms underlying such devastating neurological and psychiatric symptoms remain unclear. Here we investigated the long-term changes in neural behavior and brain structural abnormalities in a rat model of GWI. GWI is linked to exposure to GWI-related organophosphate chemicals (pyridostigmine bromide or PB and insecticide DEET, permethrin) during the stressful Gulf war.
To mimic GWI, we generated an experimental GWI prototype in rats by daily exposure to GWI-related chemicals with restraint stress (GWIR-CS) for 4 weeks. Changes in MRI scan and cognitive function were assessed at 5- and 10- months post-exposure.
In MRI scans, rats displayed significant increases in lateral ventricle T2 relaxation times at both 5- and 10-months after GWIR-CS, indicating alterations in the cerebrospinal fluid (CSF) density. Furthermore, at 10 months, there were significant decreases in the volumes of the hippocampus and thalamus and an increase in the lateral ventricle volume. At both time points, they exhibited impairments in multiple neurobehavioral tests, confirming substantial deficits in memory and mood function. GWI-CS rats also displayed aggressive behavior and a marked decrease in social interaction and forced swimming, indicating depression.
These results confirm that chronic GWIR-CS exposure led to cognitive and psychiatric symptoms with concurrent neuroimaging abnormalities in CSF, with morphological neural lesions, demonstrating the role of divergent etiological mechanisms in GWI and its comorbidities.
海湾战争综合征（GWI）是一种多症状疾病，会使退伍军人出现认知和情绪障碍，导致身体衰弱。GWI与癫痫一样，是由化学神经毒性引起的，表现为神经元兴奋性紊乱。然而，这些严重的神经和精神症状背后的机制仍不清楚。在此，我们研究了GWI大鼠模型中神经行为的长期变化和脑结构异常。GWI与在压力巨大的海湾战争期间接触与GWI相关的有机磷化学物质（溴吡斯的明或PB以及杀虫剂避蚊胺、氯菊酯）有关。
为模拟GWI，我们通过对大鼠每日施加约束应激并使其接触与GWI相关的化学物质（GWIR-CS），持续4周，建立了一个实验性GWI原型。在接触后5个月和10个月时评估磁共振成像（MRI）扫描变化和认知功能。
在MRI扫描中，GWIR-CS后5个月和10个月时，大鼠侧脑室T2弛豫时间显著增加，表明脑脊液（CSF）密度发生改变。此外，在10个月时，海马体和丘脑体积显著减小，侧脑室体积增加。在两个时间点，它们在多项神经行为测试中均表现出损伤，证实记忆和情绪功能存在明显缺陷。GWI-CS大鼠还表现出攻击性行为，社交互动和强迫游泳显著减少，表明有抑郁症状。
这些结果证实，长期暴露于GWIR-CS会导致认知和精神症状，并伴有CSF神经影像学异常以及形态学神经损伤，这表明不同病因机制在GWI及其合并症中的作用。
