Blood–brain barrier dysfunction: the undervalued frontier of hypertension

Katsi, Vasiliki; Marketou, Maria; Maragkoudakis, Spyridon; Didagelos, Matthaios; Charalambous, Georgios; Parthenakis, Fragkiskos; Tsioufis, Costas; Tousoulis, Dimitrios

doi:10.1038/s41371-020-0352-2

Cited by 39 publications

(30 citation statements)

References 67 publications

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“…Alteration in glial function and morphology (i.e., astrogliosis) is associated with disease states, vasodilator dysfunction of cerebral parenchymal arterioles (Bagi et al, 2018) and cognitive dysfunction (Verkhratsky and Nedergaard, 2018). Hypertension, regarded as a chronic inflammatory state (De Miguel et al, 2015;Rodriguez-Iturbe et al, 2017), impairs one of the first barriers of brain protection, the BBB (Katsi et al, 2020;Santisteban et al, 2020). BBB dysfunction facilitates the infiltration of plasma components to the brain and the production of proinflammatory signals that lead to microglia and astrocyte activation.…”

Section: Inflammation Aberrant Astrocytic Ca 2+ and Diseasementioning

confidence: 99%

Vasculo-Neuronal Coupling and Neurovascular Coupling at the Neurovascular Unit: Impact of Hypertension

et al. 2020

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Components of the neurovascular unit (NVU) establish dynamic crosstalk that regulates cerebral blood flow and maintain brain homeostasis. Here, we describe accumulating evidence for cellular elements of the NVU contributing to critical physiological processes such as cerebral autoregulation, neurovascular coupling, and vasculoneuronal coupling. We discuss how alterations in the cellular mechanisms governing NVU homeostasis can lead to pathological changes in which vascular endothelial and smooth muscle cell, pericyte and astrocyte function may play a key role. Because hypertension is a modifiable risk factor for stroke and accelerated cognitive decline in aging, we focus on hypertension-associated changes on cerebral arteriole function and structure, and the molecular mechanisms through which these may contribute to cognitive decline. We gather recent emerging evidence concerning cognitive loss in hypertension and the link with vascular dementia and Alzheimer's disease. Collectively, we summarize how vascular dysfunction, chronic hypoperfusion, oxidative stress, and inflammatory processes can uncouple communication at the NVU impairing cerebral perfusion and contributing to neurodegeneration.

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Section: Inflammation Aberrant Astrocytic Ca 2+ and Diseasementioning

confidence: 99%

Vasculo-Neuronal Coupling and Neurovascular Coupling at the Neurovascular Unit: Impact of Hypertension

et al. 2020

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“…This result matches the different responses to elevated blood pressure in normotensive and hypertensive rats in following experiment. The hypertensive rats had higher permeability to sucrose which was absorbed more slowly by the brain, and the authors attributed this to changes in blood flow in hypertension 18 , 42 . AUC, which characterizes the contrast delay in the brain, had the highest sensitivity out of BBB permeability parameters.…”

Section: Discussionmentioning

confidence: 99%

“…BBB damage in patients with hypertension is considered to be the main mechanism for the initiation and progression of CSVD and the development of forms mixed with neurodegeneration 15 – 17 . In these cases, hypertension is both a factor in BBB damage 18 and a consequence of the damage to the cerebral autonomic centres caused by the high BBB permeability 19 .…”

Section: Introductionmentioning

confidence: 99%

Daily blood pressure profile and blood–brain barrier permeability in patients with cerebral small vessel disease

Dobrynina

Шамтиева

Кремнева

et al. 2022

Sci Rep

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Cerebral small vessel disease (CSVD) plays an important role in cognitive impairment, stroke, disability, and death. Hypertension is the main risk factor for CSVD. The use of antihypertensive therapy has not resulted in the expected decrease in CSVD complications, which may be related to the underestimation of significance of daily blood pressure profile for blood–brain barrier (BBB) permeability. 53 patients with CSVD of varying severity (mean age 60.08 ± 6.8 years, 69.8% women, subjects with treated long-standing hypertension vs. normotensive subjects − 84.8% vs. 15.2%) and 17 healthy volunteers underwent ambulatory blood pressure monitoring (ABPM) and MRI, including T1-weighted dynamic contrast-enhanced magnetic resonance imaging for assessing BBB permeability. Most of ABPM parameters in CSVD patients did not differ from controls, but were associated with the severity of white matter hyperintensity (WMH) and the total CSVD score. BBB permeability in normal-appearing white matter (NAWM) and grey matter (GM) was significantly higher in CSVD patients, and the severity of BBB permeability remained similar in patients with different stages of WMH. Among BBB permeability parameters, the area under the curve, corresponding to an increase in the contrast transit time in NAWM, had the greatest number of correlations with deviations of ABPM parameters. BBB permeability in CSVD is a universal mechanism of NAWM and GM damage associated with a slight increase in ABPM parameters. It is obvious that the treatment of hypertension in patients with not severe WMH should be more aggressive and carried out under the control of ABPM.

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“…Ang II has hydrophilic features; therefore, it does not cross the BBB. Although, elevated circulating levels of Ang II in certain pathologic conditions, such as hypertension, provoke disruption of the BBB integrity, allowing access to circulating Ang II (Katsi et al, 2020). Evidence "suggests that peripheral and local RAS, via disruption of the BBB may promote exacerbated sympatho-excitatory activity and neurogenic hypertension" (Katsi et al, 2020).…”

Section: Systemic Renin-angiotensin System and Covid-19-associated Ne...mentioning

confidence: 99%

Role of the renin-angiotensin system in the development of COVID-19-associated neurological manifestations

Méndez-García

Escobedo

Minguer-Uribe

et al. 2022

Front. Cell. Neurosci.

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SARS-CoV-2 causes COVID-19, which has claimed millions of lives. This virus can infect various cells and tissues, including the brain, for which numerous neurological symptoms have been reported, ranging from mild and nonlife-threatening (e.g., headaches, anosmia, dysgeusia, and disorientation) to severe and life-threatening symptoms (e.g., meningitis, ischemic stroke, and cerebral thrombosis). The cellular receptor for SARS-CoV-2 is angiotensinconverting enzyme 2 (ACE2), an enzyme that belongs to the renin-angiotensin system (RAS). RAS is an endocrine system that has been classically associated with regulating blood pressure and fluid and electrolyte balance; however, it is also involved in promoting inflammation, proliferation, fibrogenesis, and lipogenesis. Two pathways constitute the RAS with counter-balancing effects, which is the key to its regulation. The first axis (classical) is composed of angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and angiotensin type 1 receptor (AT1R) as the main effector, which -when activated-increases the production of aldosterone and antidiuretic hormone, sympathetic nervous system tone, blood pressure, vasoconstriction, fibrosis, inflammation, and reactive oxygen species (ROS) production. Both systemic and local classical RAS' within the brain are associated with cognitive impairment, cell death, and inflammation. The second axis (non-classical or alternative) includes ACE2, which converts Ang II to Ang-(1-7), a peptide molecule that activates Mas receptor (MasR) in charge of opposing Ang II/AT1R actions. Thus, the alternative RAS axis enhances cognition, synaptic remodeling, cell survival, cell signal transmission, and antioxidant/anti-inflammatory mechanisms in the brain. In a physiological state, both RAS axes remain balanced. However, some Frontiers in Cellular Neuroscience 01 frontiersin.org Méndez-García et al. 10.3389/fncel.2022.977039factors can dysregulate systemic and local RAS arms. The binding of SARS-CoV-2 to ACE2 causes the internalization and degradation of this enzyme, reducing its activity, and disrupting the balance of systemic and local RAS, which partially explain the appearance of some of the neurological symptoms associated with COVID-19. Therefore, this review aims to analyze the role of RAS in the development of the neurological effects due to SARS-CoV-2 infection. Moreover, we will discuss the RAS-molecular targets that could be used for therapeutic purposes to treat the short and long-term neurological COVID-19-related sequelae.

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Blood–brain barrier dysfunction: the undervalued frontier of hypertension

Cited by 39 publications

References 67 publications

Vasculo-Neuronal Coupling and Neurovascular Coupling at the Neurovascular Unit: Impact of Hypertension

Vasculo-Neuronal Coupling and Neurovascular Coupling at the Neurovascular Unit: Impact of Hypertension

Daily blood pressure profile and blood–brain barrier permeability in patients with cerebral small vessel disease

Role of the renin-angiotensin system in the development of COVID-19-associated neurological manifestations

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