scholarly journals Deciphering the Role of Extracellular Vesicles Derived from ZIKV-Infected hcMEC/D3 Cells on the Blood–Brain Barrier System

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2363
Author(s):  
Antonios Fikatas ◽  
Jonas Dehairs ◽  
Sam Noppen ◽  
Jordi Doijen ◽  
Frank Vanderhoydonc ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Extracellular Vesicles ◽  
Viral Infections ◽  
Brain Barrier ◽  
Label Free ◽  
Blood Brain ◽  
Lipid Species ◽  
The Central Nervous System ◽  
Viral Components

To date, no vaccines or antivirals are available against Zika virus (ZIKV). In addition, the mechanisms underlying ZIKV-associated pathogenesis of the central nervous system (CNS) are largely unexplored. Getting more insight into the cellular pathways that ZIKV recruits to facilitate infection of susceptible cells will be crucial for establishing an effective treatment strategy. In general, cells secrete a number of vesicles, known as extracellular vesicles (EVs), in response to viral infections. These EVs serve as intercellular communicators. Here, we investigated the role of EVs derived from ZIKV-infected human brain microvascular endothelial cells on the blood–brain barrier (BBB) system. We demonstrated that ZIKV-infected EVs (IEVs) can incorporate viral components, including ZIKV RNA, NS1, and E-protein, and further transfer them to several types of CNS cells. Using label-free impedance-based biosensing, we observed that ZIKV and IEVs can temporally disturb the monolayer integrity of BBB-mimicking cells, possibly by inducing structural rearrangements of the adherent protein VE-cadherin (immunofluorescence staining). Finally, differences in the lipidomic profile between EVs and their parental cells possibly suggest a preferential sorting mechanism of specific lipid species into the vesicles. To conclude, these data suggest that IEVs could be postulated as vehicles (Trojan horse) for ZIKV transmission via the BBB.

Disruption of the Blood-Brain Barrier by Extracellular Vesicles From Preeclampsia Plasma and Hypoxic Placentae: Attenuation by Magnesium Sulfate

Hypertension ◽  
2021 ◽  
Author(s):  
José León ◽  
Jesenia Acurio ◽  
Lina Bergman ◽  
Juán López ◽  
Anna Karin Wikström ◽  
...  
Keyword(s):  
Magnesium Sulfate ◽  
Blood Brain Barrier ◽  
Extracellular Vesicles ◽  
Normal Pregnancy ◽  
Brain Barrier ◽  
Cell Monolayers ◽  
Cerebrovascular Complications ◽  
Blood Brain

Preeclampsia, a pregnancy-related endothelial disorder, is associated with both cardiovascular and cerebrovascular complications. Preeclampsia requires the presence of a placenta as part of its pathophysiology, yet the role of this organ in the cerebrovascular complications remains unclear. Research has shown that circulating small extracellular vesicles (also known as exosomes) present in preeclampsia plasma can generate endothelial dysfunction, but it is unclear whether the impairment of function of brain endothelial cells at the blood-brain barrier is secondary to plasma-derived or placental-derived exosomes. In this study, we evaluated the effect of small extracellular vesicles isolated from plasma samples of women with preeclampsia (n=12) and women with normal pregnancy (n=11) as well as from human placental explants from normotensive pregnancies (n=6) subjected to hypoxia (1% oxygen) on the integrity of the blood-brain barrier, using both in vitro and animal models. Exposure of human-derived brain endothelial cell monolayers to plasma and plasma-derived small extracellular vesicles from preeclamptic pregnancies increased the permeability and reduced the transendothelial electrical resistance. A similar outcome was observed with hypoxic placental-derived small extracellular vesicles, which also increased the permeability to Evan’s blue in the brain of C57BL6 nonpregnant mice. Cotreatment with magnesium sulfate reversed the effects elicited by plasma, plasma-derived, and hypoxic placental-derived small extracellular vesicles in the employed models. Thus, circulating small extracellular vesicles in plasma from women with preeclampsia or from hypoxic placentae disrupt the blood-brain barrier, which can be prevented using magnesium sulfate. These findings provide new insights into the pathophysiology of cerebral complications associated with preeclampsia.

Role of the Blood–Brain Barrier in the Nutrition of the Central Nervous System

2014 ◽  
Vol 45 (8) ◽  
pp. 610-638 ◽  
Author(s):  
Patricia Campos-Bedolla ◽  
Fruzsina R. Walter ◽  
Szilvia Veszelka ◽  
Mária A. Deli
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
The Central Nervous System

scholarly journals Role of the Extracellular Traps in Central Nervous System

2021 ◽  
Vol 12 ◽  
Author(s):  
Xinyan Wu ◽  
Hanhai Zeng ◽  
Lingxin Cai ◽  
Gao Chen
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Immune Cells ◽  
Brain Barrier ◽  
Extracellular Traps ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Extracellular Trap

It has been reported that several immune cells can release chromatin and granular proteins into extracellular space in response to the stimulation, forming extracellular traps (ETs). The cells involved in the extracellular trap formation are recognized including neutropils, macrophages, basophils, eosinophils, and mast cells. With the development of research related to central nervous system, the role of ETs has been valued in neuroinflammation, blood–brain barrier, and other fields. Meanwhile, it has been found that microglial cells as the resident immune cells of the central nervous system can also release ETs, updating the original understanding. This review aims to clarify the role of the ETs in the central nervous system, especially in neuroinflammation and blood–brain barrier.

scholarly journals The Role of Heparin and Glycocalyx in Blood–Brain Barrier Dysfunction

2021 ◽  
Vol 12 ◽  
Author(s):  
Rui Yang ◽  
Mingming Chen ◽  
Jiayin Zheng ◽  
Xin Li ◽  
Xiaojuan Zhang
Keyword(s):  
Blood Brain Barrier ◽  
Vascular Endothelial Cells ◽  
Neurological Diseases ◽  
Brain Dysfunction ◽  
Brain Barrier ◽  
Endothelial Glycocalyx ◽  
Barrier Dysfunction ◽  
Blood Brain ◽  
The Central Nervous System

The blood-brain barrier (BBB) functions as a dynamic boundary that protects the central nervous system from blood and plays an important role in maintaining the homeostasis of the brain. Dysfunction of the BBB is a pathophysiological characteristic of multiple neurologic diseases. Glycocalyx covers the luminal side of vascular endothelial cells(ECs). Damage of glycocalyx leads to disruption of the BBB, while inhibiting glycocalyx degradation maintains BBB integrity. Heparin has been recognized as an anticoagulant and it protects endothelial glycocalyx from destruction. In this review, we summarize the role of glycocalyx in BBB formation and the therapeutic potency of heparin to provide a theoretical basis for the treatment of neurological diseases related to BBB breakdown.

scholarly journals Size-selective opening of the blood–brain barrier by targeting endothelial sphingosine 1–phosphate receptor 1

2017 ◽  
Vol 114 (17) ◽  
pp. 4531-4536 ◽  
Author(s):  
Keisuke Yanagida ◽  
Catherine H. Liu ◽  
Giuseppe Faraco ◽  
Sylvain Galvani ◽  
Helen K. Smith ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Inflammation ◽  
Brain Barrier ◽  
The Novel ◽  
Object Recognition Test ◽  
Blood Brain ◽  
Sphingosine 1 Phosphate ◽  
The Central Nervous System ◽  
G Protein Coupled

The vasculature of the central nervous system (CNS) forms a selective barrier termed the blood–brain barrier (BBB). Disruption of the BBB may contribute to various CNS diseases. Conversely, the intact BBB restricts efficient penetration of CNS-targeted drugs. Here, we report the BBB-regulatory role of endothelial sphingosine 1–phosphate (S1P) receptor-1, a G protein-coupled receptor known to promote the barrier function in peripheral vessels. Endothelial-specific S1pr1 knockout mice (S1pr1iECKO) showed BBB breach for small-molecular-mass fluorescence tracers (<3 kDa), but not larger tracers (>10 kDa). Chronic BBB leakiness was associated with cognitive impairment, as assessed by the novel object recognition test, but not signs of brain inflammation. Brain microvessels of S1pr1iECKO mice showed altered subcellular distribution of tight junctional proteins. Pharmacological inhibition of S1P1 function led to transient BBB breach. These data suggest that brain endothelial S1P1 maintain the BBB by regulating the proper localization of tight junction proteins and raise the possibility that endothelial S1P1 inhibition may be a strategy for transient BBB opening and delivery of small molecules into the CNS.

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