Protective effects of edaravone on white matter pathology in a novel mouse model of Alzheimer's disease with chronic cerebral hypoperfusion
Protective effects of edaravone on white matter pathology in a novel mouse model of Alzheimer's disease with chronic cerebral hypoperfusion
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DOI：
10.1177/0271678x20968927
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发表时间：
2021-06-01
影响因子：
6.3
通讯作者：
Abe, Koji
中科院分区：
文献类型：
--
作者：
Feng, Tian;Yamashita, Toru;Abe, Koji
脑慢性低灌注（CCH）引起的白色病变（WML）可能参与阿尔茨海默病（AD）的病理生理过程。然而，潜在的机制和治疗方法尚未完全确定。在本研究中，我们研究了自由基清除剂依达拉奉（EDA）对我们先前报道的AD（APP 23）加CCH运动和认知缺陷的新小鼠模型中WML的潜在治疗作用。相对于12个月龄（M）的AD伴CCH小鼠，EDA通过改善白色物质完整性的破坏、增强少突胶质细胞祖细胞的增殖、减弱内皮/星形胶质细胞单位功能障碍以及减少神经炎症和氧化应激，强烈改善了12个月龄（M）的APP 23小鼠胼胝体中CCH诱导的WML。目前的研究表明，EDA的长期管理可能会提供一个有前途的治疗方法，在AD加CCH疾病的认知缺陷的WML。
White matter lesions (WMLs) caused by cerebral chronic hypoperfusion (CCH) may contribute to the pathophysiology of Alzheimer's disease (AD). However, the underlying mechanisms and therapeutic approaches have yet to be totally identified. In the present study, we investigated a potential therapeutic effect of the free radical scavenger edaravone (EDA) on WMLs in our previously reported novel mouse model of AD (APP23) plus CCH with motor and cognitive deficits. Relative to AD with CCH mice at 12 months (M) of age, EDA strongly improved CCH-induced WMLs in the corpus callosum of APP23 mice at 12 M by improving the disruption of white matter integrity, enhancing the proliferation of oligodendrocyte progenitor cells, attenuating endothelium/astrocyte unit dysfunction, and reducing neuroinflammation and oxidative stress. The present study demonstrates that the long-term administration of EDA may provide a promising therapeutic approach for WMLs in AD plus CCH disease with cognitive deficits.