科研成果详情

题名2-BFI protects against ischemic stroke by selectively acting on NR2B-containing NMDA receptors
作者
发表日期2024-12-15
发表期刊Brain Research   影响因子和分区
语种英语
原始文献类型Article
关键词2-BFI Excitotoxicity Ischemic stroke NMDA receptor Patch-clamp
摘要Background and purpose: The intricate roles of NMDA receptors, specifically those containing the NR2A or NR2B subunit, in ischemic stroke pathology necessitate targeted therapeutic investigations. Building on our prior discovery showcasing the neuroprotective potential of 2-(benzofuran-2-yl)-2-imidazoline (2-BFI), an imidazoline I2 receptor ligand, in inhibiting NMDA receptor currents during ischemic stroke, this study aims to elucidate the specific impact of 2-BFI on NR2A- and NR2B-containing NMDARs. Experimental approach: Through whole-cell patch-clamp techniques, we observed an inhibition by 2-BFI on NR2A-containing NMDAR currents (IC50 = 238.6 μM) and NR2B-containing NMDAR currents (IC50 = 18.47 μM). Experiments with HEK293 cells expressing exogenous receptor subunits revealed a significantly higher affinity of 2-BFI towards NR2B-containing NMDARs. In vivo studies involved the co-administration of 2-BFI and the NR2A subunit antagonist NVP-AAM077 in rats subjected to transient middle cerebral artery occlusion (tMCAO). Key results 2-BFI exhibited a pronounced preference for inhibiting NR2B-containing NMDAR currents, leading to a notable mitigation of cerebral ischemic injury when administered in conjunction with NVP-AAM077 in the tMCAO rat model. Furthermore, alterations in the expression of downstream proteins specific to NR2B-containing NMDA receptors were observed, suggesting targeted molecular effects. Conclusion and implications This study unveils the neuroprotective potential of 2-BFI in ischemic stroke by selectively inhibiting NR2B-containing NMDA receptors. These findings lay the foundation for precise therapeutic strategies, showcasing the differential roles of NR2A and NR2B subunits and paving the way for advancements in targeted interventions for ischemic stroke treatment.
ISSN0006-8993
EISSN1872-6240
卷号1845
DOI10.1016/j.brainres.2024.149284
收录类别SCOPUS ; PUBMED
URL查看原文
PubMed ID39423961
SCOPUSEID2-s2.0-85206906604
通讯作者地址[Han, Zhao]Department of Neurology,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Zhejiang Province,Wenzhou,325000,China
Scopus学科分类Neuroscience (all);Molecular Biology;Neurology (clinical);Developmental Biology
SCOPUS_IDSCOPUS_ID:85206906604
引用统计
文献类型期刊论文
条目标识符https://kms.wmu.edu.cn/handle/3ETUA0LF/220926
专题第二临床医学院、附属第二医院、育英儿童医院
附属第二医院
附属台州医院
其他_附属台州医院(浙江省台州医院)
通讯作者Han, Zhao
作者单位
1.Department of Neurology,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou,China;
2.Department of Critical Care Medicine,Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University,Taizhou,China
第一作者单位第二临床医学院,附属第二医院、育英儿童医院;  附属第二医院;  附属台州医院(浙江省台州医院);  附属台州医院
通讯作者单位第二临床医学院,附属第二医院、育英儿童医院;  附属第二医院
第一作者的第一单位第二临床医学院,附属第二医院、育英儿童医院
推荐引用方式
GB/T 7714
Xu, Shasha,Chen, Jiaou,Xu, Chunfei,et al. 2-BFI protects against ischemic stroke by selectively acting on NR2B-containing NMDA receptors[J]. Brain Research,2024,1845.
APA Xu, Shasha., Chen, Jiaou., Xu, Chunfei., Xu, Ye., Xu, Lu., ... & Han, Zhao. (2024). 2-BFI protects against ischemic stroke by selectively acting on NR2B-containing NMDA receptors. Brain Research, 1845.
MLA Xu, Shasha,et al."2-BFI protects against ischemic stroke by selectively acting on NR2B-containing NMDA receptors".Brain Research 1845(2024).

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