2-(2-Benzofuranyl)-2-Imidazoline Attenuates the Disruption of the Blood–Brain Barrier in EAE via NMDAR
NEUROCHEMICAL RESEARCH(2021)
摘要
Blood–brain barrier (BBB) disruption has been recognized as an early hallmark of multiple sclerosis (MS) pathology. Our previous studies have shown that 2-(2-Benzofuranyl)-2-imidazoline (2-BFI) protected against experimental autoimmune encephalomyelitis (EAE), a classic animal model of MS. However, the potential effects of 2-BFI on BBB permeability have not yet been evaluated in the context of EAE. Herein, we aimed to investigate the effect of 2-BFI on BBB permeability in both an animal model and an in vitro BBB model using TNF-α to imitate the inflammatory damage to the BBB in MS. In the animal model, 2-BFI reduced neurological deficits and BBB permeability in EAE mice compared with saline treatment. The Western blot results indicated that 2-BFI not only alleviated the loss of the tight junction protein occludin caused by EAE but also inhibited the activation of the NR1-ERK signaling pathway. In an in vitro BBB model, 2-BFI (100 μM) alleviated the TNF-α-induced increase in permeability and reduction in expression of occludin in monolayer bEnd.3 cells. Similar protective effects were also observed after treatment with the NMDAR antagonist MK801. The Western blot results showed that the TNF-α-induced BBB breakdown and increase in NMDAR subunit 1 (NR1) levels and ERK phosphorylation could be blocked by pretreatment with 2-BFI or MK801. However, no additional effect was observed on BBB permeability or the expression of occludin and p-ERK after pretreatment with both 2-BFI and MK801. Our study indicates that 2-BFI alleviates the disruption of BBB in the context of inflammatory injury similar to that of MS by targeting NMDAR1, as well as by likely activating the subsequent ERK signaling pathway. These results provide further evidence for 2-BFI as a potential drug for the treatment of MS.
更多查看译文
关键词
2-BFI, MK801, NMDAR, Blood–, brain barrier, Multiple sclerosis
AI 理解论文
溯源树
样例
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要