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Selective white matter abnormalities in a novel rat model of vascular dementia

Lookup NU author(s): Professor Raj KalariaORCiD, Dr Kazuo Washida, Dr Masafumi Ihara


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Rats subjected to bilateral common carotid artery (CCA) occlusion or 2-vessel occlusion (2VO) have been used as animal models of subcortical ischemic vascular dementia. However, this model possesses an inherent limitation in that cerebral blood flow (CBF) drops too sharply and substantially after ligation of CCAs. To circumvent such hypoxic-ischemic conditions, we tested implantation of the ameroid constrictor device on bilateral CCAs of male Wistar-Kyoto rats and more precisely replicated chronic cerebral hypoperfusion by gradual narrowing of the CCAs (2-vessel gradual occlusion; 2VGO). The acute cerebral blood flow reduction and resultant inflammatory responses observed in the 2VO rats were eliminated in the 2VGO rats. Thus, chronic cerebral hypoperfusion was segregated, and induced selective white matter changes with relatively preserved neurovascular coupling and substantially less metabolic and histological derangements in the gray matter including the hippocampus. This led to significant spatial working memory impairment of a magnitude similar to the 2VO rats at 28 days postoperation. The 2VGO model may more closely mimic cognitive impairment subsequent to selective white matter damage. (C) 2012 Elsevier Inc. All rights reserved.

Publication metadata

Author(s): Kitamura A, Fujita Y, Oishi N, Kalaria RN, Washida K, Maki T, Okamoto Y, Hase Y, Yamada M, Takahashi J, Ito H, Tomimoto H, Fukuyama H, Takahashi R, Ihara M

Publication type: Article

Publication status: Published

Journal: Neurobiology of Aging

Year: 2012

Volume: 33

Issue: 5

Pages: 1012.e25

Print publication date: 30/11/2011

ISSN (print): 0197-4580

ISSN (electronic): 1558-1497

Publisher: Elsevier Inc.


DOI: 10.1016/j.neurobiolaging.2011.10.033


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