Vascular change and opposing effects of the angiotensin type 2 receptor in a mouse model of vascular cognitive impairment

Füchtemeier, Martina and Brinckmann, Marie P. and Foddis, Marco and Kunz, Alexander and Po, Chrystelle and Curato, Caterina and Dirnagl, Ulrich and Farr, Tracy D. (2015) Vascular change and opposing effects of the angiotensin type 2 receptor in a mouse model of vascular cognitive impairment. Journal of Cerebral Blood Flow & Metabolism, 35 (3). pp. 476-484. ISSN 1559-7016

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Abstract

Our aims were to assess the spatiotemporal development of brain pathology in a mouse model of chronic hypoperfusion using magnetic resonance imaging (MRI), and to test whether the renin-angiotensin system (RAS) can offer therapeutic benefit. For the first time, different patterns of cerebral blood flow alterations were observed in hypoperfused mice that ranged from an immediate and dramatic to a delayed decrease in cerebral perfusion. Diffusion tensor imaging revealed increases in several quantitative parameters in different brain regions that are indicative of white-matter degeneration; this began around 3 weeks after induction of hypoperfusion. While this model may be more variable than previously reported, neuroimaging tools represent a promising way to identify surrogate markers of pathology. Vascular remodelling was observed in hypoperfused mice, particularly in the anterior part of the Circle of Willis. While the angiotensin II receptor type 2 agonist, Compound 21 (C21), did not influence this response, it did promote expansion of the basilar artery in microcoil animals. Furthermore, C21-treated animals exhibited increased brain lymphocyte infiltration, and importantly, C21 had opposing effects on spatial reference memory in hypoperfused and sham mice. These results suggest that the RAS may have a role in vascular cognitive impairment.

Item Type: Article
Keywords: Angiotensin II receptor type 2; Diffusion tensor imaging; Mouse hypoperfusion; Perfusion weighted imaging; Vascular cognitive impairment
Schools/Departments: University of Nottingham UK Campus > Faculty of Medicine and Health Sciences > School of Life Sciences
Identification Number: https://doi.org/10.1038/jcbfm.2014.221
Depositing User: Eprints, Support
Date Deposited: 15 Apr 2016 12:55
Last Modified: 14 Sep 2016 15:28
URI: http://eprints.nottingham.ac.uk/id/eprint/32792

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