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Published on: September 28, 2015
Structural and functional brain alterations in a murine model of Angiotensin II-induced hypertension
Anja Meissner1,2, Jens Minnerup2, Guadalupe Soria1
1Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Insights
Hypertension significantly contributes to cerebral small vessel disease (cSVD) and cognitive decline. This study developed a mouse model of Angiotensin II-induced hypertension, proving effective for studying early-onset cSVD and vascular cognitive impairment.
Area of Science:
- Neuroscience
- Cardiovascular Research
- Animal Models
Background:
- Hypertension is a primary risk factor for cerebral small vessel disease (cSVD), stroke, and vascular dementia.
- Current understanding of cSVD pathogenesis and effective treatments is limited, hindering therapeutic development.
- Existing animal models, particularly mouse models, inadequately represent cSVD and associated cognitive impairments.
Purpose of the Study:
- To characterize hypertension-induced cerebrovascular changes and cognitive consequences in a novel mouse model.
- To evaluate the utility of this model for studying early-onset cSVD and vascular cognitive impairment.
- To establish a suitable mouse model for investigating pathologies preceding vascular dementia.
Main Methods:
- Adult wild-type mice (C57BL/6N) were treated with Angiotensin II (AngII) and L-NAME for 4 weeks to induce hypertension.
- Cerebrovascular alterations, structural changes, and functional consequences were assessed.
- The impact of preventing blood pressure elevation on cSVD development and cognitive decline was investigated.
Main Results:
- Combined AngII and L-NAME treatment induced hypertension with cerebral alterations resembling early-onset cSVD.
- Additional AngII bolus injections led to vascular cognitive impairment.
- Preventing hypertension effectively protected against cSVD symptoms and cognitive decline.
Conclusions:
- This Angiotensin II-induced hypertension mouse model accurately recapitulates key features of early-onset cSVD and vascular cognitive impairment.
- The model provides a valuable tool for studying the pathogenesis of cSVD and developing interventions for vascular cognitive impairment.
- Controlling blood pressure is crucial for preventing cSVD and associated cognitive deficits.
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.
