Disruption of White Matter Integrity by Chronic Cerebral Hypoperfusion in Alzheimer’s Disease Mouse Model

2016 ◽  
Vol 52 (4) ◽  
pp. 1311-1319 ◽  
Author(s):  
Yun Zhai ◽  
Toru Yamashita ◽  
Yumiko Nakano ◽  
Zhuoran Sun ◽  
Ryuta Morihara ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Mouse Model ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
White Matter Integrity

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

2020 ◽  
pp. 0271678X2096892
Author(s):  
Tian Feng ◽  
Toru Yamashita ◽  
Ryo Sasaki ◽  
Koh Tadokoro ◽  
Namiko Matsumoto ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Mouse Model ◽  
Cognitive Deficits ◽  
Cerebral Hypoperfusion ◽  
Radical Scavenger ◽  
Protective Effects ◽  
Model Of Alzheimer’S Disease ◽  
Promising Therapeutic Approach

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.

Axon–glial disruption: the link between vascular disease and Alzheimer's disease?

2011 ◽  
Vol 39 (4) ◽  
pp. 881-885 ◽  
Author(s):  
Karen Horsburgh ◽  
Michell M. Reimer ◽  
Philip Holland ◽  
Guiquan Chen ◽  
Gillian Scullion ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Cognitive Decline ◽  
Vascular Dysfunction ◽  
Critical Role ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Early Event ◽  
Published Data

Vascular risk factors play a critical role in the development of cognitive decline and AD (Alzheimer's disease), during aging, and often result in chronic cerebral hypoperfusion. The neurobiological link between hypoperfusion and cognitive decline is not yet defined, but is proposed to involve damage to the brain's white matter. In a newly developed mouse model, hypoperfusion, in isolation, produces a slowly developing and diffuse damage to myelinated axons, which is widespread in the brain, and is associated with a selective impairment in working memory. Cerebral hypoperfusion, an early event in AD, has also been shown to be associated with white matter damage and notably an accumulation of amyloid. The present review highlights some of the published data linking white matter disruption to aging and AD as a result of vascular dysfunction. A model is proposed by which chronic cerebral hypoperfusion, as a result of vascular factors, results in both the generation and accumulation of amyloid and injury to white matter integrity, resulting in cognitive impairment. The generation of amyloid and accumulation in the vasculature may act to perpetuate further vascular dysfunction and accelerate white matter pathology, and as a consequence grey matter pathology and cognitive decline.

Chronic Cerebral Hypoperfusion Accelerates Alzheimer’s Disease Pathology with Cerebrovascular Remodeling in a Novel Mouse Model

2016 ◽  
Vol 53 (3) ◽  
pp. 893-905 ◽  
Author(s):  
Yun Zhai ◽  
Toru Yamashita ◽  
Yumiko Nakano ◽  
Zhuoran Sun ◽  
Jingwei Shang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion

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

2019 ◽  
Vol 71 (1) ◽  
pp. 327-339 ◽  
Author(s):  
Tian Feng ◽  
Toru Yamashita ◽  
Jingwei Shang ◽  
Xiaowen Shi ◽  
Yumiko Nakano ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion

scholarly journals Lipid Peroxidation in Chronic Cerebral HypoperfusionInduced Neurodegeneration in Rats

2020 ◽  
Vol 10 (2) ◽  
Author(s):  
Anil Kumar S ◽  
Saif SA ◽  
Oothuman P ◽  
Mustafa MIA
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lipid Peroxidation ◽  
Neurodegenerative Disorders ◽  
Neuronal Damage ◽  
Neuronal Cell ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Control Group ◽  
Vessel Occlusion

Introduction: Reduced cerebral blood fl ow is associated with neurodegenerative disorders and dementia, in particular. Experimental evidence has demonstrated the initiating role of chronic cerebral hypoperfusion in neuronal damage to the hippocampus, the cerebral cortex, the white matter areas and the visual system. Permanent, bilateral occlusion of the common carotid arteries of rats (two vessel occlusion - 2VO) has been introduced for the reproduction of chronic cerebral hypoperfusion as it occurs in Alzheimer’s disease and human aging. Increased generation of free radicals through lipid peroxidation can damage neuronal cell membrane. Markers of lipid peroxidation have been found to be elevated in brain tissues and body fl uids in neurodegenerative diseases, including Alzheimer’s disease, Parkinson disease and amyotrophic lateral sclerosis. Materials and Methods: Malondialdehyde (MDA), final product of lipid peroxidation, was estimated by thiobarbituric acid-reactive substances (TBARS) assay kit at eight weeks after induction of 2VO in the rats and control group. Results: Our study revealed a highly signifi cant (p<0.001) increase in the mean MDA concentration (12.296 ± 1.113 μM) in 2VO rats as compared to the control group (5.286 ± 0.363 μM) rats. Conclusion: Therapeutic strategies to modulate lipid peroxidation early throughout the course of the disease may be promising in slowing or possibly preventing neurodegenerative disorders.

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