Structural and functional brain alterations in a murine model of Angiotensin II-induced hypertension

TY - JOUR

T1 - Structural and functional brain alterations in a murine model of Angiotensin II-induced hypertension

AU - Meissner, Anja

AU - Minnerup, Jens

AU - Soria, Guadalupe

AU - Planas, Anna M.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

U2 - 10.1111/jnc.13905

DO - 10.1111/jnc.13905

M3 - Article

C2 - 27874975

VL - 140

SP - 509

EP - 521

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 1471-4159

IS - 3

ER -