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

详细信息	查看全文 | 推荐本文 |

• 作者：Akihiro Kitamura^a ; Youshi Fujita^a ; Naoya Oishi^b ; Raj N. Kalaria^c ; Kazuo Washida^a ; Takakuni Maki^a ; Yoko Okamoto^a ; Yoshiki Hase^a ; Mahito Yamada^a ; Jun Takahashi^d ; Hidefumi Ito^a ; Hidekazu Tomimoto^e ; Hidenao Fukuyama^b ; Ryosuke Takahashi^a ; Masafumi Ihara^a ; ^{ihara@kuhp.kyoto-u.ac.jp}
• 关键词：Vascular dementia ; Chronic cerebral hypoperfusion ; Ameroid constrictor ; White matter change ; Rat ; Neurovascular coupling
• 刊名：Neurobiology of Aging
• 出版年：2012
• 期刊代码：202_01974580
• 类别：med
• 出版时间：May, 2012
• 卷：33
• 期：5
• 页码：1012.e25-1012.e35
• 文件大小：3314 K

摘要

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; ). The acute cerebral blood flow reduction and resultant inflammatory responses observed in the 2VO rats were eliminated in the 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 model may more closely mimic cognitive impairment subsequent to selective white matter damage.