Protective effects of edaravone on white matter pathology in a novel mouse model of Alzheimer’s disease with chronic cerebral hypoperfusion

Tian Feng, Toru Yamashita, Ryo Sasaki, Koh Tadokoro, Namiko Matsumoto, Nozomi Hishikawa, Koji Abe

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1437-1448
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Volume41
Issue number6
DOIs
Publication statusPublished - Jun 2021
Externally publishedYes

Keywords

  • Alzheimer’s disease
  • chronic cerebral hypoperfusion
  • edaravone
  • mouse model
  • white matter

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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