Skip to main content

Research Repository

Advanced Search

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

F�chtemeier, Martina; Brinckmann, Marie P.; Foddis, Marco; Kunz, Alexander; Po, Chrystelle; Curato, Caterina; Dirnagl, Ulrich; Farr, Tracy D.

Authors

Martina F�chtemeier

Marie P. Brinckmann

Marco Foddis

Alexander Kunz

Chrystelle Po

Caterina Curato

Ulrich Dirnagl

Tracy D. Farr



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.

Citation

Füchtemeier, M., Brinckmann, M. P., Foddis, M., Kunz, A., Po, C., Curato, C., …Farr, T. 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 and Metabolism, 35(3), https://doi.org/10.1038/jcbfm.2014.221

Journal Article Type Article
Acceptance Date Nov 10, 2014
Online Publication Date Dec 10, 2014
Publication Date Mar 1, 2015
Deposit Date Apr 15, 2016
Publicly Available Date Mar 28, 2024
Journal Journal of Cerebral Blood Flow & Metabolism
Print ISSN 0271-678X
Electronic ISSN 1559-7016
Publisher SAGE Publications
Peer Reviewed Peer Reviewed
Volume 35
Issue 3
DOI https://doi.org/10.1038/jcbfm.2014.221
Keywords Angiotensin II receptor type 2; Diffusion tensor imaging; Mouse hypoperfusion; Perfusion weighted imaging;
Vascular cognitive impairment
Public URL https://nottingham-repository.worktribe.com/output/984606
Publisher URL http://dx.doi.org/10.1038/jcbfm.2014.221

Files





You might also like



Downloadable Citations