Zhang Fan, Zhang Cong, Sun Wei, Xie Shuhua, Wu Pengcheng, Zeng Guoyong, Liu Xianghong
Department of Neurology, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, 341000, China.
J Mol Neurosci. 2025 Mar 19;75(2):38. doi: 10.1007/s12031-025-02332-9.
Autoimmune encephalitis (AE) is an immune-mediated non-infectious disease, and novel and robust biomarkers are needed to improve the diagnosis and prognostic outcomes of AE. Oxidative stress is a ubiquitous cellular process causing damage to various biological molecules. The aim of our study was to understand the clinical implication and mechanism underlying oxidative stress in AE. Liquid chromatography-mass spectrometry analysis was conducted on the serum of eight patients with AE and seven healthy controls, and oxidative stress was characterized. Experimental autoimmune encephalitis (EAE) models were established in C57BL/6 and SJL mice for investigation of the therapeutic effect and mechanism of anti-oxidative stress N-acetylcysteine (NAC). We provided proteomic landscape in the serum of AE and identified antioxidant ALB, APOE, GPX3, and SOD3 as serum diagnostic markers of AE. The antioxidant markers were lowly expressed both in the serum of AE patients and central nervous system (CNS) of EAE mice. NAC administration improved clinical signs and motor function and alleviated nerve injury of EAE mice as well as lowered oxidative stress (decreased MDA content and ROS accumulation and elevated SOD activity and GSH content). ALB, APOE, GPX3, and SOD3 expressions were elevated by NAC in the CNS of EAE mice. Moreover, NAC reduced tissue-resident CD4 and CD8 T cells and GFAP-marked astrocytes and Iba-1-marked microglia in EAE mice, thus alleviating autoimmunity-mediated damage and neuroinflammation. Our findings facilitate the discovery of novel oxidative stress-related biomarkers for AE and reveal the promise of anti-oxidative stress for AE management.
自身免疫性脑炎（AE）是一种免疫介导的非感染性疾病，需要新的强有力的生物标志物来改善AE的诊断和预后。氧化应激是一种普遍存在的细胞过程，会对各种生物分子造成损害。我们研究的目的是了解AE中氧化应激的临床意义和潜在机制。对8例AE患者和7例健康对照者的血清进行液相色谱-质谱分析，以表征氧化应激。在C57BL/6和SJL小鼠中建立实验性自身免疫性脑脊髓炎（EAE）模型，以研究抗氧化应激剂N-乙酰半胱氨酸（NAC）的治疗效果和机制。我们提供了AE患者血清中的蛋白质组图谱，并鉴定出抗氧化剂ALB、APOE、GPX3和SOD3作为AE的血清诊断标志物。这些抗氧化标志物在AE患者血清和EAE小鼠中枢神经系统（CNS）中均低表达。给予NAC可改善EAE小鼠的临床症状和运动功能，减轻神经损伤，并降低氧化应激（降低丙二醛含量和活性氧积累，提高超氧化物歧化酶活性和谷胱甘肽含量）。NAC可提高EAE小鼠中枢神经系统中ALB、APOE、GPX3和SOD3的表达。此外，NAC可减少EAE小鼠组织驻留的CD4和CD8 T细胞以及胶质纤维酸性蛋白标记的星形胶质细胞和离子钙结合衔接分子1标记的小胶质细胞，从而减轻自身免疫介导的损伤和神经炎症。我们的研究结果有助于发现与AE相关的新型氧化应激生物标志物，并揭示抗氧化应激在AE治疗中的前景。
