Enduring brain dysfunction is amid the highly manifested symptoms in veterans with Gulf War Illness (GWI). Animal studies have established that lasting brain dysfunction in GWI is concomitant with augmented oxidative stress, inflammation, and declined neurogenesis in the brain, and systemic inflammation. We hypothesize that drugs capable of restoring redox homeostasis in GWI will improve cognitive and mood function with modulation of neuroinflammation and neurogenesis. We examined the efficacy of monosodium luminol-GVT (MSL), a drug that promotes redox homeostasis, for improving cognitive and mood function in GWI rats. Young rats were exposed to GWI-related chemicals and moderate restraint stress for four weeks. Four months later, GWI rats received different doses of MSL or vehicle for eight weeks. Behavioral analyses in the last three weeks of treatment revealed that GWI rats receiving higher doses of MSL displayed better cognitive and mood function associated with reinstatement of redox homeostasis. Such restoration was evident from the normalized expression of multiple genes encoding proteins involved in combating oxidative stress in the brain and the return of several oxidative stress markers to control levels in the brain and the circulating blood. Sustained redox homeostasis by MSL also resulted in antiinflammatory and pro-neurogenic effects, which were apparent from reduced densities of hypertrophied astrocytes and activated microglia, and increased neurogenesis with augmented neural stem cell proliferation. Moreover, MSL treatment normalized the concentration of multiple proinflammatory markers in the circulating blood. Thus, MSL treatment reinstated redox homeostasis in an animal model of GWI, which resulted in alleviation of both brain and systemic inflammation, improved neurogenesis, and better cognitive and mood function.

患有海湾战争疾病（GWI）的退伍军人中表现出明显症状的是持久的脑功能障碍。动物研究已经确定，GWI中持久的脑功能障碍会伴随氧化应激增加，炎症，大脑神经发生能力下降和全身性炎症。我们假设能够在GWI中恢复氧化还原稳态的药物将通过调节神经炎症和神经发生来改善认知和情绪功能。我们研究了鲁米诺-GVT单钠盐（MSL）（一种促进氧化还原稳态的药物）改善GWI大鼠认知和情绪功能的功效。幼鼠暴露于与GWI相关的化学物质和适度的束缚压力四个星期。四个月后，GWI大鼠接受了不同剂量的MSL或赋形剂八周。在治疗的最后三周进行的行为分析显示，接受更高剂量的MSL的GWI大鼠表现出更好的认知和情绪功能，与恢复氧化还原稳态有关。从多个基因的正常表达中可以明显看出这种恢复，这些基因编码了与抗击大脑中的氧化应激有关的蛋白质，并使几种氧化应激标记物返回到控制大脑和循环血液中的水平。MSL维持的氧化还原稳态也导致抗炎和促神经源性作用，这从肥大的星形胶质细胞和活化的小胶质细胞密度降低以及神经发生增加和神经干细胞增殖增加中可以明显看出。此外，MSL治疗使循环血液中多种促炎标记物的浓度正常化。因此，