Clinical and Pathological Benefits of Edaravone for Alzheimer's Disease with Chronic Cerebral Hypoperfusion in a Novel Mouse Model

Tian Feng, Toru Yamashita, Jingwei Shang, Xiaowen Shi, Yumiko Nakano, Ryuta Morihara, Keiichiro Tsunoda, Emi Nomura, Ryo Sasaki, Koh Tadokoro, Namiko Matsumoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

Research output: Contribution to journalArticle

Abstract

Alzheimer's disease (AD) and chronic cerebral hypoperfusion (CCH) often coexist in dementia patients in aging societies. The hallmarks of AD including amyloid-β (Aβ)/phosphorylated tau (pTau) and pathology-related events such as neural oxidative stress and neuroinflammation play critical roles in pathogenesis of AD with CCH. A large number of lessons from failures of drugs targeting a single target or pathway on this so complicated disease indicate that disease-modifying therapies targeting multiple key pathways hold potent potential in therapy of the disease. In the present study, we used a novel mouse model of AD with CCH to investigate a potential therapeutic effect of a free radical scavenger, Edaravone (EDA) on AD with CCH via examining motor and cognitive capacity, AD hallmarks, neural oxidative stress, and neuroinflammation. Compared with AD with CCH mice at 12 months of age, EDA significantly improved motor and cognitive deficits, attenuated neuronal loss, reduced Aβ/pTau accumulation, and alleviated neural oxidative stress and neuroinflammation. These findings suggest that EDA possesses clinical and pathological benefits for AD with CCH in the present mouse model and has a potential as a therapeutic agent for AD with CCH via targeting multiple key pathways of the disease pathogenesis.

Original languageEnglish
Pages (from-to)327-339
Number of pages13
JournalJournal of Alzheimer's Disease
Volume71
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Alzheimer Disease
Oxidative Stress
phenylmethylpyrazolone
Free Radical Scavengers
Therapeutic Uses
Drug Delivery Systems
Amyloid
Dementia
Therapeutics
Pathology

Keywords

  • Alzheimer's disease
  • chronic cerebral hypoperfusion
  • edaravone
  • neural oxidative stress
  • neuroinflammation
  • neuronal loss

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Clinical and Pathological Benefits of Edaravone for Alzheimer's Disease with Chronic Cerebral Hypoperfusion in a Novel Mouse Model. / Feng, Tian; Yamashita, Toru; Shang, Jingwei; Shi, Xiaowen; Nakano, Yumiko; Morihara, Ryuta; Tsunoda, Keiichiro; Nomura, Emi; Sasaki, Ryo; Tadokoro, Koh; Matsumoto, Namiko; Hishikawa, Nozomi; Ohta, Yasuyuki; Abe, Koji.

In: Journal of Alzheimer's Disease, Vol. 71, No. 1, 01.01.2019, p. 327-339.

Research output: Contribution to journalArticle

Feng, Tian ; Yamashita, Toru ; Shang, Jingwei ; Shi, Xiaowen ; Nakano, Yumiko ; Morihara, Ryuta ; Tsunoda, Keiichiro ; Nomura, Emi ; Sasaki, Ryo ; Tadokoro, Koh ; Matsumoto, Namiko ; Hishikawa, Nozomi ; Ohta, Yasuyuki ; Abe, Koji. / Clinical and Pathological Benefits of Edaravone for Alzheimer's Disease with Chronic Cerebral Hypoperfusion in a Novel Mouse Model. In: Journal of Alzheimer's Disease. 2019 ; Vol. 71, No. 1. pp. 327-339.
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