Gulf War Illness (GWI) is a chronic multisymptomatic disorder that afflicts over 1/3rd of the 1991 GW veterans. It spans multiple bodily systems and presents itself as a syndrome exhibiting diverse symptoms including fatigue, depression, mood, and memory and concentration deficits, musculoskeletal pain and gastrointestinal distress in GW veterans. The etiology of GWI is complex and many factors, including chemical, physiological, and environmental stressors present in the GW arena, have been implicated for its development. It has been over 30 years since the end of the GW but, GWI has been persistent in suffering veterans who are also dealing with paucity of effective treatments. The multifactorial aspect of GWI along with genetic heterogeneity and lack of available data surrounding war-time exposures have proved to be challenging in developing pre-clinical models of GWI. Despite this, over a dozen GWI animal models exist in the literature. In this article, following a brief discussion of GW history, GWI definitions, and probable causes for its pathogenesis, we will expand upon various experimental models used in GWI laboratory research. These animal models will be discussed in the context of their attempts at mimicking GW-related exposures with regards to the variations in chemical combinations, doses, and frequency of exposures. We will discuss their advantages and limitations in modeling GWI followed by a discussion of behavioral and molecular findings in these models. The mechanistic data obtained from these preclinical studies have offered multiple molecular pathways including chronic inflammation, mitochondrial dysfunction, oxidative stress, lipid disturbances, calcium homeostatic alterations, changes in gut microbiota, and epigenetic modifications, amongst others for explaining GWI development and its persistence. Finally, these findings have also informed us on novel druggable targets in GWI. While, it has been difficult to conceive a single pre-clinical model that could express all the GWI signs and exhibit biological complexity reflective of the clinical presentation in GWI, animal models have been critical for identifying molecular underpinnings of GWI and evaluating treatment strategies for GWI.

海湾战争疾病 (GWI) 是一种慢性多症状疾病，影响 1991 年 GW 退伍军人的 1/3 以上。它跨越多个身体系统，表现为一种综合征，表现出多种症状，包括 GW 退伍军人的疲劳、抑郁、情绪、记忆力和注意力缺陷、肌肉骨骼疼痛和胃肠道不适。GWI 的病因很复杂，许多因素，包括 GW 领域中存在的化学、生理和环境压力源，都与其发展有关。自 GW 结束以来已经 30 多年了，但是，GWI 一直在忍受同样缺乏有效治疗的退伍军人的痛苦。GWI 的多因素方面以及遗传异质性和缺乏有关战时暴露的可用数据已证明在开发 GWI 的临床前模型方面具有挑战性。尽管如此，文献中仍存在十几种 GWI 动物模型。在本文中，在简要讨论 GW 历史、GWI 定义及其发病机制的可能原因之后，我们将扩展 GWI 实验室研究中使用的各种实验模型。这些动物模型将在他们尝试模拟 GW 相关暴露的背景下进行讨论，其中涉及化学组合、剂量和暴露频率的变化。我们将讨论它们在 GWI 建模中的优势和局限性，然后讨论这些模型中的行为和分子发现。从这些临床前研究中获得的机制数据提供了多种分子途径，包括慢性炎症、线粒体功能障碍、氧化应激、脂质紊乱、钙稳态改变、肠道菌群变化和表观遗传修饰等，用于解释 GWI 的发展及其持续性。最后，这些发现也让我们了解了 GWI 中的新药物靶点。虽然很难构想出一个可以表达所有 GWI 体征并表现出反映 GWI 临床表现的生物学复杂性的单一临床前模型，但动物模型对于确定 GWI 的分子基础和评估 GWI 的治疗策略至关重要. 氧化应激、脂质紊乱、钙稳态改变、肠道微生物群的变化和表观遗传修饰等，用于解释 GWI 的发展及其持续性。最后，这些发现也让我们了解了 GWI 中的新药物靶点。虽然很难构想出一个可以表达所有 GWI 体征并表现出反映 GWI 临床表现的生物学复杂性的单一临床前模型，但动物模型对于确定 GWI 的分子基础和评估 GWI 的治疗策略至关重要. 氧化应激、脂质紊乱、钙稳态改变、肠道微生物群的变化和表观遗传修饰等，用于解释 GWI 的发展及其持续性。最后，这些发现也让我们了解了 GWI 中的新药物靶点。虽然很难构想出一个可以表达所有 GWI 体征并表现出反映 GWI 临床表现的生物学复杂性的单一临床前模型，但动物模型对于确定 GWI 的分子基础和评估 GWI 的治疗策略至关重要. 这些发现也让我们了解了 GWI 中的新药物靶点。虽然很难构想出一个可以表达所有 GWI 体征并表现出反映 GWI 临床表现的生物学复杂性的单一临床前模型，但动物模型对于确定 GWI 的分子基础和评估 GWI 的治疗策略至关重要. 这些发现也让我们了解了 GWI 中的新药物靶点。虽然很难构想出一个可以表达所有 GWI 体征并表现出反映 GWI 临床表现的生物学复杂性的单一临床前模型，但动物模型对于确定 GWI 的分子基础和评估 GWI 的治疗策略至关重要.