Pathophysiology of blood brain barrier dysfunction during chronic cerebral hypoperfusion in vascular cognitive impairment

Abstract

The prevalence of cerebrovascular disease increases with age, placing the elderly at a greater lifetime risk for dementia. Vascular cognitive impairment (VCI) encompasses a spectrum of cognitive deficits from mild cognitive impairment to dementia. VCI and its most severe form, vascular dementia (VaD), is becoming a major public health concern worldwide. As growing efforts are being taken to understand VCI and VaD in animal models and humans, the pathogenesis of the disease is being actively explored. It is postulated that chronic cerebral hypoperfusion (CCH) is a major cause of VCI. CCH activates a molecular and cellular injury cascade that leads to breakdown of the blood brain barrier (BBB) and neurodegeneration. The BBB tightly regulates the movement of substances between the blood and the brain, thereby regulating the microenvironment within the brain parenchyma. Here we illustrate how BBB damage is causal in the pathogenesis of VCI through the increased activation of pathways related to excitotoxicity, oxidative stress, inflammation and matrix metalloproteinases that lead to downstream perivascular damage, leukocyte infiltration and white matter changes in the brain. Thus, CCH-induced BBB damage may initiate and contribute to a vicious cycle, resulting in progressive neuropathological changes of VCI in the brain. This review outlines the molecular and cellular mechanisms that govern BBB breakdown during CCH and highlights the clinical evidence in identifying at-risk VCI patients.

Cerrahi Menopoz ve Kronik Serebral Hipoperfüzyon Oluşturulmuş Sıçanlarda Spironolaktonun Prefrontal Korteks ve Göz Dokularında Glikojen ve Oksidatif Stres Parametreleri Üzerine Etkisi

“…Serbest radikaller ve antioksidan sistem arasındaki dengesizliğin neden olduğu oksidatif stres çeşitli hastalıkların patolojik sürecinde yer aldığı kabul edilmektedir (1). Özellikle beyin çoklu doymamış yağ asitleri bakımından zengindir, büyük miktarlarda oksijen tüketir ve homeostazı sürdürmek için büyük miktarlarda ATP gerektirir, bu nedenle oksidatif hasara karşı hassastır.…”

“…Med J West Black Sea 2022;6(2): 177-185 GİRİŞ Kronik serebral hipoperfüzyon (KSH) vasküler demans ve Alzheimer hastalığı (AD) gibi çeşitli nörodejeneratif hastalıklarda yaygın bir patolojik mekanizmadır. Yapılan çalışmalar KSH'un glial aktivasyonu, reaktif oksijen türlerinin (ROS) oluşumunu, mitokondrial disfonksiyonu, nöroinflamasyonu, kan beyin bariyeri (KBB) hasarını, beyaz cevher lezyonunu, tau hiperfosforilasyonunu, amiloid beta (Aβ) birikimini artırarak nörodejenerasyona ve sonuçta da nöronal hasara yol açabileceğini göstermektedir (1,2). Ayrıca bu değişiklikler öğrenme ve hafızayla ilişkili hipokampüs ve prefrontal korteks (PFC)'de anormal beyin yapısı ve işlevine yol açarak bilişsel bozulmaya neden olmaktadır (3,4).…”

“…Hipoksik-iskemik beyin ve retina hasarının gelişiminde ve ilerlemesinde enerji metabolizmasının bozulması ve oksidatif stres oluşumu önemli rol oynar (1). Normal beyin aktivitesi esas olarak astrositlerin metabolik plastisitesine bağlıdır ve sadece kandan glukoz tedarikini değil, aynı zamanda beyindeki spesifik aktiviteyi besleyen astrositlerde depolanan glikojeni de gerektirir (9).…”

Initial and ongoing tobacco smoking elicits vascular damage and distinct inflammatory response linked to neurodegeneration

“…The effects by smoking that cause dementia varies from toxic to vascular damage (Livingston et al 2020). It has been widely described that chronic endothelial damage leads to blood-brain barrier dysfunction and consequent neuroinflammation (Wardlaw et al 2017; Rajeev et al 2022). There is a long list of biomarker candidates being considered; however, knowing the role that chronic cigarette smoking has in the presentation of vascular dementia, we aimed to study the plasma levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and brain-derived neurotrophic factor (BDNF) in asymptomatic chronic smokers.…”

Angiogenesis and Multiple Sclerosis Pathogenesis: A Glance at New Pharmaceutical Approaches

“…It allows the passage of water, some gases, and lipid-soluble molecules by passive diffusion, as well as the selective transport of molecules such as glucose and amino acids that are crucial for neural function. Thus, for the most part, the BBB prevents the movement of substances from the blood to brain tissues [ 10 , 11 ]. In MS, BBB function fails because of a dysregulated paracellular permeability due to the release of histamine, leukotrienes, and chemokines, which recruits neutrophils and other cells to invade CNS [ 12 ].…”