莫里斯水上航行任务
促炎细胞因子
小胶质细胞
医学
药理学
NF-κB
神经炎症
下调和上调
认知功能衰退
αBκ
癌症研究
化学
内分泌学
炎症
内科学
痴呆
海马体
生物化学
疾病
基因
作者
Lei Li,Guojun He,Mingyu Shi,Juehua Zhu,Yongqing Cheng,Yang Chen,Jin Chen,Qianfei Xue
标识
DOI:10.1016/j.ejphar.2023.176036
摘要
Cerebral small vessel disease (CSVD) is one of the most important causes of stroke and vascular dementia, so exploring effective treatment modalities for CSVD is warranted. This study aimed to explore the anti-inflammatory effects of Edaravone dexborneol (C.EDA) in a CSVD model. Mice with CSVD showed distinct cognitive decline, as assessed by the Morris water maze (MWM). Pathological staining verified leakage across the blood‒brain barrier (BBB), microglial proliferation, neuronal loss and demyelination. Western blot analysis demonstrated that M1 microglia dominated prophase and released proinflammatory molecules; the aryl hydrocarbon receptor (AHR) was found to participate in modulating nuclear factor-kappa B (NF-κB) signalling activation through tumour necrosis factor receptor-associated factor-6 (TRAF6). C.EDA treatment resulted in the polarization of microglia from the M1 to the M2 phenotype. Mice sequentially treated with C.EDA exhibited a significant improvement in cognitive function; expression of the anti-inflammatory cytokines and modulatory proteins AHR and TRAF6 was upregulated, while the levels of pNF-κBp65 and pIΚBα were downregulated. C.EDA promoted microglial activation towards the M2 phenotype by upregulating AHR expression, which prevented TRAF6 ubiquitination, promoted NF-κB RelA/p65 protein degradation and inhibited subsequent NF-κB phosphorylation. Mechanistically, the anti-inflammatory effect of C.EDA alleviated neuronal loss and myelin damage, while at the functional level, C.EDA improved cognitive function and thus showed good application prospects.
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