Xinshubao tablet rescues cognitive dysfunction in a mouse model of vascular dementia: Involvement of neurogenesis and neuroinflammation - 29/02/24
Abstract |
Vascular dementia (VaD) represents a severe cognitive dysfunction syndrome closed linked to cardiovascular function. In the present study, we assessed the potential of Xinshubao tablet (XSB), a traditional Chinese prescription widely used for cardiovascular diseases, to mitigate neuropathological damage in a mouse model of VaD and elucidated the underlying mechanisms. Our findings revealed that oral administration of XSB rescued the cardiac dysfunction resulting from bilateral common carotid artery stenosis (BCAS), improved the cerebral blood flow (CBF) and cognitive function, reduced white matter injury, inhibited excessive microglial and astrocytic activation, stimulated hippocampal neurogenesis, and reduced neural apoptosis in the brains of BCAS mice. Mechanistically, RNA-seq analysis indicated that XSB treatment was significantly associated with neuroinflammation, vasculature development, and synaptic transmission, which were further confirmed by q-PCR assays. Western blot results revealed that XSB treatment hindered the nuclear translocation of nuclear factor-κB (NF-κB), thereby suppressing the NF-κB signaling pathway. These results collectively demonstrated that XSB could ameliorate cognitive dysfunction caused by BCAS through regulating CBF, reducing white matter lesions, suppressing glial activation, promoting neurogenesis, and mitigating neuroinflammation. Notably, the NF-κB signaling pathway emerged as a pivotal player in this mechanism.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Highlights |
• | XSB rescues cognitive dysfunction and multifaceted neuropathologic damage in mice with VaD. |
• | The NF-κB pathway plays a vital role in XSB treatment against VaD. |
• | Improving cardiac function emerges as a potential therapeutic advantage in VaD. |
Abbreviations : VaD, AD, XSB, IF, MWM, q-PCR, RNA-seq, UPLC-Q-TOF-MS/MS, TIC, BCAS, CBF, WMLs, EdU, GFAP, NeuN, Iba-1, Sox-2, NF-κB, IKKα, MBP, H&E, TUNEL, CCA, i.g., i.p., NSCs, PFA, LFB, TEM, EF, FS, DEGs, PCA, GO, KEGG, PPI, ROS, BBB, BSA, SD, ANOVA
Keywords : Vascular dementia, Chronic cerebral hypoperfusion, Xinshubao tablet, White matter damage, Neurogenesis, NF-κB signaling pathway
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Vol 172
Article 116219- mars 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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