Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450002, People's Republic of China.
Henan Key Laboratory of Tumor Pathology, Zhengzhou 450002, People's Republic of China.
Aging (Albany NY). 2021 May 24;13(10):14001-14014. doi: 10.18632/aging.203009.
Vascular dementia (VaD) is the second most common type of dementia worldwide. Although there are five FDA-approved drugs for the treatment of Alzheimer's disease (AD), none of them have been applied to treat VaD. Adalimumab is a TNF-α inhibitor that is used for the treatment of autoimmune diseases such as rheumatoid arthritis. In a recent retrospective case-control study, the application of adalimumab for rheumatoid or psoriasis was shown to decrease the risk of AD. However, whether adalimumab can be used for the treatment of VaD is not clear. In this study, we used 2VO surgery to generate a VaD rat model and treated the rats with adalimumab or vehicle. We demonstrated that VaD rats treated with adalimumab exhibited significant improvements in memory. In addition, adalimumab treatment significantly alleviated neuronal loss in the hippocampi of VaD rats. Moreover, adalimumab significantly reduced microglial activation and reversed M1/M2 polarization in VaD rats. Furthermore, adalimumab treatment suppressed the activity of NF-κB, an important neuroinflammatory transcription factor. Finally, adalimumab displayed a protective role against oxidative stress in VaD rats. Our results indicate that adalimumab may be applied for the treatment of human patients with VaD.
血管性痴呆（VaD）是全球第二常见的痴呆症类型。虽然有五种经美国食品和药物管理局（FDA）批准用于治疗阿尔茨海默病（AD）的药物，但没有一种药物被应用于治疗 VaD。阿达木单抗是一种 TNF-α 抑制剂，用于治疗类风湿关节炎等自身免疫性疾病。最近的一项回顾性病例对照研究表明，阿达木单抗用于治疗类风湿关节炎或银屑病可降低 AD 的风险。然而，阿达木单抗是否可用于治疗 VaD 尚不清楚。在这项研究中，我们使用 2VO 手术制作 VaD 大鼠模型，并使用阿达木单抗或载体对大鼠进行治疗。我们证明，接受阿达木单抗治疗的 VaD 大鼠的记忆功能有显著改善。此外，阿达木单抗治疗显著减轻了 VaD 大鼠海马区的神经元丢失。此外，阿达木单抗显著抑制了 VaD 大鼠中小胶质细胞的激活和 M1/M2 极化的逆转。此外，阿达木单抗治疗抑制了 NF-κB 的活性，NF-κB 是一种重要的神经炎症转录因子。最后，阿达木单抗在 VaD 大鼠中发挥了对抗氧化应激的保护作用。我们的研究结果表明，阿达木单抗可能可用于治疗人类 VaD 患者。
