title: Selective white matter abnormalities in a novel rat model of vascular dementia.
abstract: 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.
authors: Department of Neurology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors: Akihiro
authors: A
authors: Kitamura
authors: Youshi
authors: Y
authors: Fujita
authors: Naoya
authors: N
authors: Oishi
authors: Raj N
authors: RN
authors: Kalaria
authors: Kazuo
authors: K
authors: Washida
authors: Takakuni
authors: T
authors: Maki
authors: Yoko
authors: Y
authors: Okamoto
authors: Yoshiki
authors: Y
authors: Hase
authors: Mahito
authors: M
authors: Yamada
authors: Jun
authors: J
authors: Takahashi
authors: Hidefumi
authors: H
authors: Ito
authors: Hidekazu
authors: H
authors: Tomimoto
authors: Hidenao
authors: H
authors: Fukuyama
authors: Ryosuke
authors: R
authors: Takahashi
authors: Masafumi
authors: M
authors: Ihara
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation / Q000502:physiology; D015140:Dementia, Vascular / Q000000981:diagnostic imaging / Q000401:mortality / Q000503:physiopathology*; D004195:Disease Models, Animal; D056784:Leukoencephalopathies / Q000000981:diagnostic imaging / Q000401:mortality / Q000503:physiopathology*; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D011877:Radionuclide Imaging; D051381:Rats; D011921:Rats, Inbred WKY