Anti-NMDAR antibodies, the blood-brain barrier, and anti-NMDAR encephalitis

Xiarong Gong; Niya Wang; Hongyan Zhu; Ning Tang; Kunhua Wu; Qiang Meng

doi:10.3389/fneur.2023.1283511

Anti-NMDAR antibodies, the blood-brain barrier, and anti-NMDAR encephalitis

Front Neurol. 2023 Dec 8:14:1283511. doi: 10.3389/fneur.2023.1283511. eCollection 2023.

Authors

Xiarong Gong^{1

2}, Niya Wang³, Hongyan Zhu⁴, Ning Tang³, Kunhua Wu², Qiang Meng³

Affiliations

¹ Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China.
² Department of MR, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China.
³ Department of Neurology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China.
⁴ Department of Clinical Laboratory, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China.

Abstract

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an antibody-related autoimmune encephalitis. It is characterized by the existence of antibodies against NMDAR, mainly against the GluN1 subunit, in cerebrospinal fluid (CSF). Recent research suggests that anti-NMDAR antibodies may reduce NMDAR levels in this disorder, compromising synaptic activity in the hippocampus. Although anti-NMDAR antibodies are used as diagnostic indicators, the origin of antibodies in the central nervous system (CNS) is unclear. The blood-brain barrier (BBB), which separates the brain from the peripheral circulatory system, is crucial for antibodies and immune cells to enter or exit the CNS. The findings of cytokines in this disorder support the involvement of the BBB. Here, we aim to review the function of NMDARs and the relationship between anti-NMDAR antibodies and anti-NMDAR encephalitis. We summarize the present knowledge of the composition of the BBB, especially by emphasizing the role of BBB components. Finally, we further provide a discussion on the impact of BBB dysfunction in anti-NMDAR encephalitis.

Keywords: NMDAR receptor; anti-NMDAR encephalitis; autoimmune disorder; blood–brain barrier; neurovascular unit.

Publication types

Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (no. 81960228), Yunnan Health Training Project of High Level Talents (no. H-2019070), and Yunnan Provincial Basic Research-General Program (no. 202101AT070235). The funders provide the paper submission fee and the follow-up experiments.