Mouse models of cerebral injury and cognitive impairment in hypertension

Perrotta, Marialuisa; Carnevale, Daniela; Carnevale, Lorenzo

doi:10.3389/fnagi.2023.1199612

Cited by 3 publications

(2 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 177 Available models can, however, be used to differentiate the effects of hypertension from atherosclerosis and investigate AD‐related processes (reviewed in Ref. 178 ) (Table 3 ). In C57Bl/6J (wild‐type) mice, hypertension due to transverse aortic constriction causes brain Aβ deposition, triggers proinflammatory cytokine production, and impairs cognition.…”

Section: Cardiometabolic Modifiable Risk Factorsmentioning

confidence: 99%

Experimental laboratory models as tools for understanding modifiable dementia risk

Sinclair,

Canty,

Ziebell

et al. 2024

Alzheimer's & Dementia

View full text Add to dashboard Cite

Experimental laboratory research has an important role to play in dementia prevention. Mechanisms underlying modifiable risk factors for dementia are promising targets for dementia prevention but are difficult to investigate in human populations due to technological constraints and confounds. Therefore, controlled laboratory experiments in models such as transgenic rodents, invertebrates and in vitro cultured cells are increasingly used to investigate dementia risk factors and test strategies which target them to prevent dementia. This review provides an overview of experimental research into 15 established and putative modifiable dementia risk factors: less early‐life education, hearing loss, depression, social isolation, life stress, hypertension, obesity, diabetes, physical inactivity, heavy alcohol use, smoking, air pollution, anesthetic exposure, traumatic brain injury, and disordered sleep. It explores how experimental models have been, and can be, used to address questions about modifiable dementia risk and prevention that cannot readily be addressed in human studies.Highlights Modifiable dementia risk factors are promising targets for dementia prevention. Interrogation of mechanisms underlying dementia risk is difficult in human populations. Studies using diverse experimental models are revealing modifiable dementia risk mechanisms. We review experimental research into 15 modifiable dementia risk factors. Laboratory science can contribute uniquely to dementia prevention.

show abstract

Section: Cardiometabolic Modifiable Risk Factorsmentioning

confidence: 99%

Experimental laboratory models as tools for understanding modifiable dementia risk

Sinclair,

Canty,

Ziebell

et al. 2024

Alzheimer's & Dementia

View full text Add to dashboard Cite

show abstract

“…Several animal models of hypertension allowed investigation of the effects of high blood pressure on the brain and provided valuable knowledge of the potential mechanisms underlying cerebrovascular damage. [12][13][14][15] However, monitoring the progressive development of lesions and respective locations in the mouse brain is still difficult, suggesting the need to implement adequate investigative tools. We and others have previously shown that transverse aortic constriction (TAC) is a relevant experimental model that mechanically increases blood pressure and progressively leads to cerebral injury and cognitive impairment.…”

mentioning

confidence: 99%

Advanced Magnetic Resonance Imaging to Define the Microvascular Injury Driven by Neuroinflammation in the Brain of a Mouse Model of Hypertension

Carnevale,

Perrotta,

Mastroiacovo

et al. 2024

Hypertension

Self Cite

View full text Add to dashboard Cite

BACKGROUND: Hypertension is one of the main risk factors for dementia and cognitive impairment. METHODS: We used the model of transverse aortic constriction to induce chronic pressure overload in mice. We characterized brain injury by advanced translational applications of magnetic resonance imaging. In parallel, we analyzed peripheral target organ damage induced by chronic pressure overload by ultrasonography. Microscopical characterization of brain vasculature was performed as well, together with the analysis of immune and inflammatory markers. RESULTS: We identified a specific structural, microstructural, and functional brain injury. In particular, we highlighted a regional enlargement of the hypothalamus, microstructural damage in the white matter of the fimbria, and a reduction of the cerebral blood flow. A parallel analysis performed by confocal microscopy revealed a correspondent tissue damage evidenced by a reduction of cerebral capillary density, paired with loss of pericyte coverage. We assessed cognitive impairment and cardiac damage induced by hypertension to perform correlation analyses with the brain injury severity. At the mechanistic level, we found that CD8+T cells, producing interferon-γ, infiltrated the brain of hypertensive mice. By neutralizing this proinflammatory cytokine, we obtained a rescue of the phenotype, demonstrating their crucial role in establishing the microvascular damage. CONCLUSIONS: Overall, we have used translational tools to comprehensively characterize brain injury in a mouse model of hypertension induced by chronic pressure overload. We have identified early cerebrovascular damage in hypertensive mice, sustained by CD8+IFN-γ+T lymphocytes, which fuel neuroinflammation to establish the injury of brain capillaries.

show abstract

Imaging the cerebral vasculature at different scales: translational tools to investigate the neurovascular interfaces

Carnevale,

Lembo

2024

Cardiovascular Research

View full text Add to dashboard Cite

The improvements in imaging technology opened up the possibility to investigate the structure and function of cerebral vasculature and the neurovascular unit with unprecedented precision and gaining deep insights not only on the morphology of the vessels, but also regarding their function and regulation related to the cerebral activity. In this review we will dissect the different imaging capabilities regarding the cerebrovascular tree, the neurovascular unit and the hemodynamic response function and thus the vascular-neuronal coupling. We will discuss both clinical and preclinical setting, with a final discussion on the current scenery in cerebrovascular imaging where Magnetic Resonance Imaging and multimodal Microscopy emerge as the most potent and versatile tools respectively in the clinical and preclinical context.

show abstract

Mouse models of cerebral injury and cognitive impairment in hypertension

Cited by 3 publications

References 67 publications

Experimental laboratory models as tools for understanding modifiable dementia risk

Experimental laboratory models as tools for understanding modifiable dementia risk

Advanced Magnetic Resonance Imaging to Define the Microvascular Injury Driven by Neuroinflammation in the Brain of a Mouse Model of Hypertension

Imaging the cerebral vasculature at different scales: translational tools to investigate the neurovascular interfaces

Contact Info

Product

Resources

About