Bian Zhihong, Hu Xinran, Liu Xia, Yu Haibo, Bian Yuting, Sun Hongming, Fukui Yusuke, Morihara Ryuta, Ishiura Hiroyuki, Yamashita Toru
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Kita-ku, Okayama, Japan.
Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Alzheimers Dis. 2023;96(2):609-622. doi: 10.3233/JAD-230413.
Alzheimer's disease (AD) is characterized by cognitive dysfunction and memory loss that is accompanied by pathological changes to white matter. Some clinical and animal research revealed that AD combined with chronic cerebral hypoperfusion (CCH) exacerbates AD progression by inducing blood-brain barrier dysfunction and fibrinogen deposition. Rivaroxaban, an anticoagulant, has been shown to reduce the rates of dementia in atrial fibrillation patients, but its effects on white matter and the underlying mechanisms are unclear.
The main purpose of this study was to explore the therapeutic effect of rivaroxaban on the white matter of AD+CCH mice.
In this study, the therapeutic effects of rivaroxaban on white matter in a mouse AD+CCH model were investigated to explore the potential mechanisms involving fibrinogen deposition, inflammation, and oxidative stress on remyelination in white matter.
The results indicate that rivaroxaban significantly attenuated fibrinogen deposition, fibrinogen-related microglia activation, oxidative stress, and enhanced demyelination in AD+CCH mice, leading to improved white matter integrity, reduced axonal damage, and restored myelin loss.
These findings suggest that long-term administration of rivaroxaban might reduce the risk of dementia.
阿尔茨海默病（AD）的特征为认知功能障碍和记忆丧失，并伴有白质的病理变化。一些临床和动物研究表明，AD合并慢性脑灌注不足（CCH）会通过诱导血脑屏障功能障碍和纤维蛋白原沉积而加剧AD的进展。利伐沙班作为一种抗凝剂，已被证明可降低心房颤动患者的痴呆发生率，但其对白质的影响及潜在机制尚不清楚。
本研究的主要目的是探讨利伐沙班对AD+CCH小鼠白质的治疗作用。
在本研究中，研究了利伐沙班对小鼠AD+CCH模型白质的治疗作用，以探讨纤维蛋白原沉积、炎症和氧化应激对白质髓鞘再生的潜在机制。
结果表明，利伐沙班可显著减轻AD+CCH小鼠的纤维蛋白原沉积、纤维蛋白原相关的小胶质细胞活化、氧化应激，并增强脱髓鞘，从而改善白质完整性，减少轴突损伤，恢复髓鞘丢失。
这些发现表明，长期服用利伐沙班可能会降低痴呆风险。
