Vascular change and opposing effects of the angiotensin type 2 receptor in a mouse model of vascular cognitive impairment.
Fiche publication
Date publication
mars 2015
Journal
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
Auteurs
Membres identifiés du Cancéropôle Est :
Dr PO Chrystelle
Tous les auteurs :
Füchtemeier M, Brinckmann MP, Foddis M, Kunz A, Po C, Curato C, Dirnagl U, Farr TD
Lien Pubmed
Résumé
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.
Mots clés
Angiotensin II Type 2 Receptor Blockers, pharmacology, Animals, Brain, drug effects, Cerebrovascular Circulation, drug effects, Dementia, Vascular, metabolism, Disease Models, Animal, Flow Cytometry, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Mice, Mice, Inbred C57BL, Receptor, Angiotensin, Type 2, metabolism
Référence
J Cereb Blood Flow Metab. 2015 Mar;35(3):476-84