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Gradual cerebral hypoperfusion in spontaneously hypertensive rats induces slowly evolving white matter abnormalities and impairs working memory

Lookup NU author(s): Yumi Yamamoto, Professor Raj KalariaORCiD, Dr Masafumi Ihara


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Rats subjected to bilateral common carotid arteries (CCAs) occlusion or 2-vessel occlusion (2VO) have been used as animal models of subcortical ischemic vascular dementia (SIVD). However, these models possess an inherent limitation in that cerebral blood flow (CBF) drops sharply and substantially after ligation of CCAs without vascular risk factors and causative small vessel changes. We previously reported a novel rat model of 2-vessel gradual occlusion (2VGO) in which ameroid constrictors (ACs) were placed bilaterally in the CCAs of Wistar-Kyoto rats. To simulate SIVD pathology more closely, we applied ACs in spontaneously hypertensive rats (SHRs), which naturally develop small vessel pathology, and compared their phenotypes with SHR-2VO and sham-operated rats. The mortality rate of the SHR-2VGO was 0% while that of the SHR-2VO was 56.5%. The CBF of the SHR-2VO dropped to 50% of the baseline level at 3h, whereas the SHR-2VGO showed a gradual CBF reduction reaching only 68% of the baseline level at seven days. The SHR-2VGO showed slowly evolving white matter abnormalities and subsequent spatial working memory impairments of a similar magnitude to the remaining SHR-2VO at 28 days. We suggest the SHR-2VGO robustly replicates selective aspects of the pathophysiology of SIVD with low mortality rate.

Publication metadata

Author(s): Kitamura A, Saito S, Maki T, Oishi N, Ayaki T, Hattori Y, Yamamoto Y, Urushitani M, Kalaria RN, Fukuyama H, Horsburgh K, Takahashi R, Ihara M

Publication type: Article

Publication status: Published

Journal: Journal of Cerebral Blood Flow and Metabolism

Year: 2016

Volume: 36

Issue: 9

Pages: 1592-1602

Print publication date: 01/09/2016

Online publication date: 13/10/2015

Acceptance date: 29/07/2015

ISSN (print): 0271-678X

ISSN (electronic): 1559-7016

Publisher: Sage Publications Ltd.


DOI: 10.1177/0271678X15606717


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Funder referenceFunder name
0605-1Ministry of Health, Labour, and Welfare