scholarly journals Nano-scale architecture of blood-brain barrier tight-junctions

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Esther Sasson ◽  
Shira Anzi ◽  
Batia Bell ◽  
Oren Yakovian ◽  
Meshi Zorsky ◽  
...  
Keyword(s):  
Tight Junctions ◽  
Blood Brain Barrier ◽  
Super Resolution ◽  
Brain Barrier ◽  
Molecular Architecture ◽  
Mouse Development ◽  
Nano Scale ◽  
Blood Brain ◽  
Structural And Functional Properties

Tight junctions (TJs) between blood-brain barrier (BBB) endothelial cells construct a robust physical barrier, whose damage underlies BBB dysfunctions related to several neurodegenerative diseases. What makes these highly specialized BBB-TJs extremely restrictive remains unknown. Here, we use super-resolution microscopy (dSTORM) to uncover new structural and functional properties of BBB TJs. Focusing on three major components, Nano-scale resolution revealed sparse (occludin) vs. clustered (ZO1/claudin-5) molecular architecture. In mouse development, permeable TJs become first restrictive to large molecules, and only later to small molecules, with claudin-5 proteins arrangement compacting during this maturation process. Mechanistically, we reveal that ZO1 clustering is independent of claudin-5 in-vivo. In contrast to accepted knowledge, we found that in the developmental context, total levels of claudin-5 inversely correlate with TJ functionality. Our super-resolution studies provide a unique perspective of BBB TJs and open new directions for understanding TJ functionality in biological barriers, ultimately enabling restoration in disease or modulation for drug delivery.

scholarly journals Nano-scale Architecture of Blood-Brain Barrier Tight-Junctions

2021 ◽  
Author(s):  
Esther Sasson ◽  
Shira Anzi ◽  
Batia Bell ◽  
Oren Yakovian ◽  
Meshi Zorsky ◽  
...  
Keyword(s):  
Tight Junctions ◽  
Blood Brain Barrier ◽  
Super Resolution ◽  
Brain Barrier ◽  
Molecular Architecture ◽  
Developmental Context ◽  
Nano Scale ◽  
Blood Brain ◽  
Structural And Functional Properties

Tight junctions (TJs) between blood-brain barrier (BBB) endothelial cells construct a robust physical barrier, whose damage underlies BBB dysfunctions related to several neurodegenerative diseases. What makes these highly specialized BBB-TJs extremely restrictive remains unknown. Here, we use super-resolution microscopy (dSTORM) to uncover new structural and functional properties of BBB TJs. Focusing on three major components, Nano-scale resolution revealed sparse (occludin) vs. clustered (ZO1/claudin-5) molecular architecture. Developmentally, permeable TJs become first restrictive to large molecules, and only later to small molecules, with claudin-5 proteins arrangement compacting during this maturation process. Mechanistically, we reveal that ZO1 clustering is independent of claudin-5 in-vivo. In contrast to accepted knowledge, we found that in the developmental context, total levels of claudin-5 inversely correlate with TJ functionality. Our super-resolution studies provide a unique perspective of BBB TJs and open new directions for understanding TJ functionality in biological barriers, ultimately enabling restoration in disease or modulation for drug delivery.

Tight junctions contain oligomeric protein assembly critical for maintaining blood–brain barrier integrity in vivo

2007 ◽  
Vol 0 (0) ◽  
pp. 071106212736002-??? ◽  
Author(s):  
Gwen McCaffrey ◽  
William D. Staatz ◽  
Carolyn A. Quigley ◽  
Nicole Nametz ◽  
Melissa J. Seelbach ◽  
...  
Keyword(s):  
Tight Junctions ◽  
Blood Brain Barrier ◽  
Protein Assembly ◽  
Brain Barrier ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Oligomeric Protein ◽  
Blood Brain Barrier Integrity

scholarly journals SARS-CoV-2 crosses the blood–brain barrier accompanied with basement membrane disruption without tight junctions alteration

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Ling Zhang ◽  
Li Zhou ◽  
Linlin Bao ◽  
Jiangning Liu ◽  
Hua Zhu ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Tight Junctions ◽  
Blood Brain Barrier ◽  
Inflammatory Responses ◽  
Vascular Wall ◽  
Brain Barrier ◽  
Inflammatory Factors ◽  
Blood Brain

AbstractSARS-CoV-2 has been reported to show a capacity for invading the brains of humans and model animals. However, it remains unclear whether and how SARS-CoV-2 crosses the blood–brain barrier (BBB). Herein, SARS-CoV-2 RNA was occasionally detected in the vascular wall and perivascular space, as well as in brain microvascular endothelial cells (BMECs) in the infected K18-hACE2 transgenic mice. Moreover, the permeability of the infected vessel was increased. Furthermore, disintegrity of BBB was discovered in the infected hamsters by administration of Evans blue. Interestingly, the expression of claudin5, ZO-1, occludin and the ultrastructure of tight junctions (TJs) showed unchanged, whereas, the basement membrane was disrupted in the infected animals. Using an in vitro BBB model that comprises primary BMECs with astrocytes, SARS-CoV-2 was found to infect and cross through the BMECs. Consistent with in vivo experiments, the expression of MMP9 was increased and collagen IV was decreased while the markers for TJs were not altered in the SARS-CoV-2-infected BMECs. Besides, inflammatory responses including vasculitis, glial activation, and upregulated inflammatory factors occurred after SARS-CoV-2 infection. Overall, our results provide evidence supporting that SARS-CoV-2 can cross the BBB in a transcellular pathway accompanied with basement membrane disrupted without obvious alteration of TJs.

16 Modulation of tight junctions in blood-brain barrier endothelium in vivo and in vitro

1996 ◽  
Vol 14 ◽  
pp. 54-54
Author(s):  
Hartwig Wolburg ◽  
Holger Gerhardt ◽  
Uwe Kniesel ◽  
Stefan Liebner ◽  
Werner Risau
Keyword(s):  
Tight Junctions ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain

Hyperosmolar blood-brain barrier disruption in baboons: an in vivo study using positron emission tomography and rubidium-82

1996 ◽  
Vol 84 (3) ◽  
pp. 494-502 ◽  
Author(s):  
Bernhard Zünkeler ◽  
Richard E. Carson ◽  
Jeffrey Olson ◽  
Ronald G. Blasberg ◽  
Mary Girton ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Brain Tumors ◽  
Blood Brain Barrier ◽  
Emission Tomography ◽  
Brain Barrier ◽  
Blood Brain ◽  
Positron Emission ◽  
The Mean ◽  
Rubidium 82

✓ Hyperosmolar blood-brain barrier (BBB) disruption remains controversial as an adjuvant therapy to increase delivery of water-soluble compounds to extracellular space in the brain in patients with malignant brain tumors. To understand the physiological effects of BBB disruption more clearly, the authors used positron emission tomography (PET) to study the time course of BBB permeability in response to the potassium analog rubidium-82 (82Rb, halflife 75 seconds) following BBB disruption in anesthetized adult baboons. Mannitol (25%) was injected into the carotid artery and PET scans were performed before and serially at 8- to 15-minute intervals after BBB disruption. The mean influx constant (K1), a measure of permeability-surface area product, in ipsilateral, mannitol-perfused mixed gray- and white-matter brain regions was 4.9 ± 2.4 µl/min/ml (± standard deviation) at baseline and increased more than 100% (ΔK1 = 9.4 ± 5.1 µl/min/ml, 18 baboons) in brain perfused by mannitol. The effect of BBB disruption on K1 correlated directly with the total amount of mannitol administered (p < 0.005). Vascular permeability returned to baseline with a halftime of 24.0 ± 14.3 minutes. The mean brain plasma volume rose by 0.57 ± 0.34 ml/100 ml in ipsilateral perfused brain following BBB disruption. This work provides a basis for the in vivo study of permeability changes induced by BBB disruption in human brain and brain tumors.

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