Georgopoulos Apostolos P, Tsilibary Effie-Photini C, Souto Eric P, James Lisa M, Engdahl Brian E, Georgopoulos Angeliki
Department of Veterans Affairs Health Care System, Brain Sciences Center, Minneapolis, Minnesota.
Department of Neuroscience, University of Minnesota Medical School, Minneapolis, Minnesota.
J Neurol Neuromedicine. 2018;3(2):19-27. doi: 10.29245/2572.942X/2018/2.1177. Epub 2018 Apr 27.
Gulf War Illness (GWI) is a chronic debilitating disease of unknown etiology that affects the brain and has afflicted many veterans of the 1990-91 Gulf War (GW). Here we tested the hypothesis that brain damage may be caused by circulating harmful substances to which GW veterans were exposed but which could not be eliminated due to lack of specific immunity. We assessed the effects of serum from GWI patients on function and morphology of brain cultures in vitro, including cultures of embryonic mouse brain and neuroblastoma N2A line. Blood serum from GWI and healthy GW veterans was added, alone and in combination, to the culture and its effects on the function and morphology of the culture assessed. Neural network function was assessed using electrophysiological recordings from multielectrode arrays in mouse brain cultures, whereas morphological assessments (neural growth and cell apoptosis) were done in neuroblastoma cultures. In contrast to healthy serum, the addition of GWI serum disrupted neural network communication and caused reduced cell growth and increased apoptosis. All of these detrimental effects were prevented or ameliorated by the concomitant addition of serum from healthy GW veterans. These findings indicate that GWI serum contains neuropathogenic factors that can be neutralized by healthy serum. We hypothesize that these factors are persistent antigens circulating in GWI blood that can be neutralized, possibly by specific antibodies present in the healthy serum, as proposed earlier.
海湾战争综合征（GWI）是一种病因不明的慢性衰弱性疾病，会影响大脑，折磨着许多1990 - 1991年海湾战争（GW）的退伍军人。在此，我们检验了一个假设，即脑损伤可能是由海湾战争退伍军人接触到的循环有害物质引起的，但由于缺乏特异性免疫力而无法消除。我们评估了海湾战争综合征患者血清对体外脑培养物功能和形态的影响，包括胚胎小鼠脑培养物和神经母细胞瘤N2A细胞系。将海湾战争综合征患者和健康海湾战争退伍军人的血清单独或联合添加到培养物中，并评估其对培养物功能和形态的影响。使用来自小鼠脑培养物中多电极阵列的电生理记录评估神经网络功能，而在神经母细胞瘤培养物中进行形态学评估（神经生长和细胞凋亡）。与健康血清相比，添加海湾战争综合征患者血清会破坏神经网络通讯，导致细胞生长减少和细胞凋亡增加。同时添加健康海湾战争退伍军人的血清可预防或改善所有这些有害影响。这些发现表明，海湾战争综合征患者血清含有可被健康血清中和的神经致病因子。我们假设这些因子是在海湾战争综合征患者血液中循环的持久性抗原，可能如之前所提出的那样，可被健康血清中存在的特异性抗体中和。
