Structural and functional brain alterations in a murine model of Angiotensin II‐induced hypertension. Issue 3 (21st December 2016)

• Record Type: Journal Article
• Authors: Meissner, Anja; Minnerup, Jens; Soria, Guadalupe; Planas, Anna M
• Is Part Of: Journal of neurochemistry. Volume 140:Issue 3(2017)
• Page Start: 509
• Page End: 521
• Publication Date: 2016-12-21
• Subjects: cerebral small vessel disease -- endothelial dysfunction -- hypertension -- microvasculature -- mouse model -- vascular dementia; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.13905
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract: Hypertension is a main risk factor for the development of cerebral small vessel disease (cSVD) – a major contributor to stroke and the most common cause of vascular dementia. Despite the increasing socioeconomic importance arising from cSVD, currently only a few specific treatment strategies with proven efficacy are known. Fundamental to the lack of specific treatments is poor understanding of the disease pathogenesis and a lack of appropriate animal models resembling all symptoms of the human disease. However, chronic hypertensive rat models have been shown to bear similarities to most key features of cSVD. Despite a significantly larger toolbox available for genotypic and phenotypic modifications compared to rats, mouse models of hypertension are unusual when modeling cSVD and associated cognitive impairment experimentally. In the present study, we therefore characterized hypertension‐mediated cerebrovascular alterations and accompanying structural and functional consequences by simultaneously treating adult wild‐type mice (C57BL/6N) with Angiotensin II (AngII) and the nitric oxide synthases inhibitor L‐NAME for 4 weeks. Hypertension associated to cerebral alterations reminiscent of early‐onset cSVD and vascular cognitive impairment when combined with additional AngII bolus injections. Most importantly, preventing the elevation of blood pressure (BP) protected from the development of cSVD symptoms and associated cognitive decline. Our data strongly support the suitability of this particular mouse model of AngII‐induced hypertension as an appropriate animal model for early‐onset cSVD and hence, vascular cognitive impairment, pathologies commonly preceding vascular dementia. Abstract : We characterized a murine model of hypertension that resembles key features of early‐onset cSVD including arteriopathy, BBB impairment, micro bleedings, incipient signs of white matter alterations, neuroinflammation and a neuropsychological profile typical for cSVD. Our data strongly support the suitability of this particular model to study underlying mechanisms of cSVD development and potential therapeutic strategies.