Neurovascular Coupling in Hypertension Is Impaired by IL-17A through Oxidative Stress.

Hypertension, a multifactorial chronic inflammatory condition, is an important risk factor for neurovascular and neurodegenerative diseases, including stroke and Alzheimer's disease. These diseases have been associated with higher concentrations of circulating interleukin (IL)-17A. However, the possible role that IL-17A plays in linking hypertension with neurodegenerative diseases remains to be established.

Targeting the blood-brain barrier disruption in hypertension by ALK5/TGF-Β type I receptor inhibitor SB-431542 and dynamin inhibitor dynasore.

Introduction: In this study, we aimed to target two molecules, transforming growth factor-beta (TGF-β) and dynamin to explore their roles in blood-brain barrier (BBB) disruption in hypertension.

Methods: For this purpose, angiotensin (ANG) II-induced hypertensive mice were treated with SB-431542, an inhibitor of the ALK5/TGF-β type I receptor, and dynasore, an inhibitor of dynamin. Albumin-Alexa fluor 594 was used to assess BBB permeability.

Cerebrospinal Fluid Biomarkers, Brain Structural and Cognitive Performances Between Normotensive and Hypertensive Controlled, Uncontrolled and Untreated 70-Year-Old Adults.

Hypertension is an important risk factor for Alzheimer's disease (AD). The pathophysiological mechanisms underlying the relationship between AD and hypertension are not fully understood, but they most likely involve microvascular dysfunction and cerebrovascular pathology. Although previous studies have assessed the impact of hypertension on different markers of brain integrity, no study has yet provided a comprehensive comparison of cerebrospinal fluid (CSF) biomarkers and structural brain differences between normotensive and hypertensive groups in a single and large cohort of older adults in relationship to cognitive performances.

Arterial stiffness and age moderate the association between physical activity and global cognition in older adults.

Background: Evidence supports that time spent on physical activity has beneficial effects on cognition in older adults. Nevertheless, whether these beneficial effects are still present at the intersection of different levels of arterial stiffness and age is uncertain.

Methods: One hundred and ten healthy older adults aged 60-75 years were examined for arterial stiffness [carotid-femoral pulse wave velocity (cf-PWV)], global cognition (composite score of Montreal Cognitive Assessment, and Mini-Mental State Examination), and self-reported physical activity (PACED diary).

Impaired Hippocampal Neurovascular Coupling in a Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD), the most common form of dementia, is characterized by neuronal degeneration and cerebrovascular dysfunction. Increasing evidence indicates that cerebrovascular dysfunction may be a key or an aggravating pathogenic factor in AD. This emphasizes the importance to investigate the tight coupling between neuronal activity and cerebral blood flow (CBF) termed neurovascular coupling (NVC).

Angiotensin II Disrupts Neurovascular Coupling by Potentiating Calcium Increases in Astrocytic Endfeet.

Background Angiotensin II (Ang II), a critical mediator of hypertension, impairs neurovascular coupling. Since astrocytes are key regulators of neurovascular coupling, we sought to investigate whether Ang II impairs neurovascular coupling through modulation of astrocytic Ca signaling. Methods and Results Using laser Doppler flowmetry, we found that Ang II attenuates cerebral blood flow elevations induced by whisker stimulation or the metabotropic glutamate receptors agonist, 1S, 3R-1-aminocyclopentane--1,3-dicarboxylic acid (<0.

Inflammation: A Mediator Between Hypertension and Neurodegenerative Diseases.

Hypertension is the most prevalent and modifiable risk factor for stroke, vascular cognitive impairment, and Alzheimer's disease. However, the mechanistic link between hypertension and neurodegenerative diseases remains to be understood. Recent evidence indicates that inflammation is a common pathophysiological trait for both hypertension and neurodegenerative diseases.

Associations Between Relative Morning Blood Pressure, Cerebral Blood Flow, and Memory in Older Adults Treated and Controlled for Hypertension.

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Bisphosphoglycerate Mutase Deficiency Protects against Cerebral Malaria and Severe Malaria-Induced Anemia.

The replication cycle and pathogenesis of the Plasmodium malarial parasite involves rapid expansion in red blood cells (RBCs), and variants of certain RBC-specific proteins protect against malaria in humans. In RBCs, bisphosphoglycerate mutase (BPGM) acts as a key allosteric regulator of hemoglobin/oxyhemoglobin. We demonstrate here that a loss-of-function mutation in the murine Bpgm (Bpgm) gene confers protection against both Plasmodium-induced cerebral malaria and blood-stage malaria.

A Cross-Sectional Study on the Impact of Arterial Stiffness on the Corpus Callosum, a Key White Matter Tract Implicated in Alzheimer's Disease.

Background: Vascular risk factors such as arterial stiffness play an important role in the etiology of Alzheimer's disease (AD), presumably due to the emergence of white matter lesions. However, the impact of arterial stiffness to white matter structure involved in the etiology of AD, including the corpus callosum remains poorly understood.

Objective: The aims of the study are to better understand the relationship between arterial stiffness, white matter microstructure, and perfusion of the corpus callosum in older adults.

Arterial stiffness cut-off value and white matter integrity in the elderly.

Objective: Central artery stiffness is a confirmed predictor of cardiovascular health status that has been consistently associated with cognitive dysfunction and dementia. The European Society of Hypertension has established a threshold of arterial stiffness above which a cardiovascular event is likely to occur. However, the threshold at which arterial stiffness alters brain integrity has never been established.

Diurnal blood pressure loads are associated with lower cognitive performances in controlled-hypertensive elderly individuals.

Introduction: Hypertension in midlife adults is associated with cognitive decline later in life. In individuals treated for hypertension, blood pressure (BP) loads have been associated with end organ damages. This study examines whether BP load inversely correlates with performance in cognitive tasks in normotensive or controlled hypertensive (CHT) individuals.

Arterial stiffness and brain integrity: A review of MRI findings.

Background: Given the increasing incidence of vascular diseases and dementia, a better understanding of the cerebrovascular changes induced by arterial stiffness is important for early identification of white and gray matter abnormalities that might antedate the appearance of clinical cognitive symptoms. Here, we review the evidence from neuroimaging demonstrating the impact of arterial stiffness on the aging brain.

Method: This review presents findings from recent studies examining the association between arterial stiffness, cognitive function, cerebral hypoperfusion, and markers of neuronal fiber integrity using a variety of MRI techniques.

Arterial Stiffness Due to Carotid Calcification Disrupts Cerebral Blood Flow Regulation and Leads to Cognitive Deficits.

Background Arterial stiffness is associated with cognitive decline and dementia; however, the precise mechanisms by which it affects the brain remain unclear. Methods and Results Using a mouse model based on carotid calcification this study characterized mechanisms that could contribute to brain degeneration due to arterial stiffness. At 2 weeks postcalcification, carotid stiffness attenuated resting cerebral blood flow in several brain regions including the perirhinal/entorhinal cortex, hippocampus, and thalamus, determined by autoradiography ( P<0.

Fully automated dual-resolution serial optical coherence tomography aimed at diffusion MRI validation in whole mouse brains.

An automated dual-resolution serial optical coherence tomography (2R-SOCT) scanner is developed. The serial histology system combines a low-resolution ( ) OCT with a high-resolution ( ) OCT to acquire whole mouse brains at low resolution and to target specific regions of interest (ROIs) at high resolution. The ROIs positions are selected either manually by the microscope operator or using an automated ROI positioning selection algorithm.

CD4 Regulatory T Lymphocytes Prevent Impaired Cerebral Blood Flow in Angiotensin II-Induced Hypertension.

Background Immune cells are key regulators of the vascular inflammatory response characteristic of hypertension. In hypertensive rodents, regulatory T lymphocytes (Treg, CD 4 CD 25) prevented vascular injury, cardiac damage, and endothelial dysfunction of mesenteric arteries. Whether Treg modulate the cerebrovascular damage induced by hypertension is unknown.

Arterial stiffness and white matter integrity in the elderly: A diffusion tensor and magnetization transfer imaging study.

Background And Purpose: The stiffness of large arteries and increased pulsatility can have an impact on the brain white matter (WM) microstructure, however those mechanisms are still poorly understood. The aim of this study was to investigate the association between central artery stiffness, axonal and myelin integrity in 54 cognitively unimpaired elderly subjects (65-75 years old).

Methods: The neuronal fiber integrity of brain WM was assessed using diffusion tensor metrics and magnetization transfer imaging as measures of axonal organization (Fractional anisotropy, Radial diffusivity) and state of myelination (Myelin volume fraction).

Sex differences in Alzheimer disease - the gateway to precision medicine.

Alzheimer disease (AD) is characterized by wide heterogeneity in cognitive and behavioural syndromes, risk factors and pathophysiological mechanisms. Addressing this phenotypic variation will be crucial for the development of precise and effective therapeutics in AD. Sex-related differences in neural anatomy and function are starting to emerge, and sex might constitute an important factor for AD patient stratification and personalized treatment.

Differential effect of angiotensin II and blood pressure on hippocampal inflammation in mice.

Background: Angiotensin II (Ang II), a peptide hormone involved in the development of hypertension, causes systemic and cerebral inflammation, affecting brain regions important for blood pressure control. The cause-and-effect relationship between hypertension and inflammation is two-way, but the role of blood pressure in the induction of cerebral inflammation is less clear. The vulnerability of specific brain regions, particularly those important for memory, is also of interest.

The many faces of vascular cognitive impairment.

This Preface introduces the articles of the special issue on "Vascular Dementia" in which several recognized experts provide an overview of this research field. The brain is a highly vascularized organ and consequently, vascular dysfunction and related pathways affect cognitive performance and memory. Vascular dementia or vascular cognitive impairment is the second most common type of dementia after Alzheimer's disease, and both disorders often occur in parallel.

Arterial stiffness, cognitive impairment and dementia: confounding factor or real risk?

Large artery stiffness is a frequent condition that arises with ageing, and is accelerated by the presence of co-morbidities like hypertension, obesity and diabetes. Although epidemiological studies have indicated an association between arterial stiffness, cognitive impairment and dementia, the precise effects of stiff arteries on the brain remains obscure. This is because, in humans, arterial stiffness is often accompanied by other factors such as age, high blood pressure, atherosclerosis and inflammation, which could themselves damage the brain independently of stiffness.

Arterial stiffness induced by carotid calcification leads to cerebral gliosis mediated by oxidative stress.

Background: Arterial stiffness is a risk factor for cognitive decline and dementia. However, its precise effects on the brain remain unexplored. Using a mouse model of carotid stiffness, we investigated its effect on glial activation and oxidative stress.