Research Paper|Volume 13, Issue 10|pp 14001—14014

Adalimumab ameliorates memory impairments and neuroinflammation in chronic cerebral hypoperfusion rats

Jing-Jing Xu^1,^2,³, Si Guo^4,^5,⁶, Rui Xue⁷, Lin Xiao^1,^2,³, Jun-Na Kou^1,^2,³, Yu-Qiong Liu^1,^2,³, Jun-Ya Han⁸, Jing-Jie Fu¹, Na Wei^1,^2,³

¹Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450002, People’s Republic of China
²Henan Key Laboratory of Tumor Pathology, Zhengzhou 450002, People’s Republic of China
³Department of Pathology, School of Basic Medicine, Zhengzhou University, Zhengzhou 450002, People’s Republic of China
⁴Department of Medical Laboratory, Henan Provincial People’s Hospital, Zhengzhou, Henan 450003, People’s Republic of China
⁵Department of Medical Laboratory of Central China Fuwai Hospital, Zhengzhou, Henan 450003, People’s Republic of China
⁶Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, Henan 450003, People’s Republic of China
⁷Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450002, People’s Republic of China
⁸Department of Pathology, People’s Hospital of Zhengzhou, Zhengzhou 450000, People’s Republic of China

* Equal contribution

Received: February 23, 2021Accepted: April 5, 2021Published: May 24, 2021

https://doi.org/10.18632/aging.203009

Copyright: © 2021 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.