A blood-brain barrier to peroxidase in capillaries surrounded by perivascular spaces

1968 ◽  
Vol 122 (2) ◽  
pp. 249-267 ◽  
Author(s):  
T. S. Bodenheimer ◽  
M. W. Brightman
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Perivascular Spaces ◽  
Blood Brain

scholarly journals SILVER DEPOSITION IN THE CENTRAL NERVOUS SYSTEM AND THE HEMATOENCEPHALIC BARRIER STUDIED WITH THE ELECTRON MICROSCOPE

1955 ◽  
Vol 1 (2) ◽  
pp. 161-166 ◽  
Author(s):  
V. L. van Breemen ◽  
C. D. Clemente
Keyword(s):  
Choroid Plexus ◽  
Blood Brain Barrier ◽  
Cell Membranes ◽  
Area Postrema ◽  
Light And Electron Microscopy ◽  
Blood Stream ◽  
Brain Barrier ◽  
Perivascular Spaces ◽  
Silver Deposition ◽  
Blood Brain

For the purpose of studying the hematoencephalic barrier as it is concerned with silver circulating in the blood stream, silver nitrate was vitally administered to rats in their drinking water over periods of 6 to 8 months. The cerebrum, cerebellum, medulla, area postrema, and choroid plexus were prepared for light and electron microscopy. Silver deposition was found in the perivascular spaces in the choroid plexus, area postrema, in the medulla surrounding the area postrema, and in minute quantities in the cerebrum, cerebellum, and most of the medulla. Two levels of the hematoencephalic barrier were apparently demonstrated in our investigations. The endothelial linings of the vessels in the cerebrum, cerebellum, and medulla constitute the first threshold of the hematoencephalic barrier (specifically here, blood-brain barrier). The cell membranes adjacent to the perivascular spaces form the second threshold, as follows:—the neuroglial cell membranes in the cerebrum, cerebellum, and medulla (blood-brain barrier); the membranes of the neuroglial cells in the area postrema (blood-brain barrier); and the membranes of the epithelial cells of the choroid plexus (blood-cerebrospinal fluid barrier). This study deals with silver deposition and does not infer that the penetration of ionic silver, if present in the blood stream, would necessarily be limited to the regions described. Bleb-like structures were observed to cover the epithelial cell surfaces in the choroid plexus. They may be cellular projections increasing the cell surface area or they may be secretory droplets.

Abstract 44: Enlarged Perivascular Spaces Correlate With CSF Biomarkers for Abnormal Blood-brain Barrier Permeability and Neuroinflammation in Patients With Vascular Cognitive Impairment

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Laith Maali ◽  
Branko Huisa ◽  
Jillian Prestopnik ◽  
Clifford Qualls ◽  
Jeffrey Thompson ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Blood Brain Barrier ◽  
Vascular Cognitive Impairment ◽  
Brain Barrier ◽  
Csf Biomarkers ◽  
Perivascular Spaces ◽  
Albumin Ratio ◽  
Blood Brain ◽  
Bbb Permeability

Background: Enlarged perivascular spaces (PVS) in the brain are common but their etiology and specificity are unclear. Multiple studies have shown a correlation between enlarged PVS and white matter hyperintensities (WMHs), but the relationship with vascular disease is uncertain. We used albumin CSF to blood ratio as a method to measure permeability of the blood-brain barrier (BBB) in patients with vascular cognitive impairment (VCI). It is possible that the enlarged PVS are associated with an increase in BBB permeability, which could interfere with perivascular fluid flow. Therefore, we hypothesized that enlarged PVS correlate with CSF markers of increased BBB permeability and neuroinflammation. Methods: We prospectively recruited 107 VCI patients with white matter disease. At entry, they had brain MRIs with standardized ranking for enlarged PVS. Sixty-one had lumbar puncture to obtain CSF for analysis of albumin ratio, matrix metalloproteinases-2 (MMP-2) index, and amyloid-beta1-42 (Abeta42). The data was analyzed statistically with nonparametric correlation methods. Results: Enlarged PVS had a positive correlation with CSF albumin ratio, which is a biomarker for increased BBB permeability ( p <0.01), and a negative correlation with the neuroinflammatory biomarker, MMP2 index ( p <0.02), and with Abeta42 ( p <0.02), which is cleared by the PVS. Conclusion: Our results suggest an association between PVS, MMP-mediated increased BBB permeability, and clearance of Abeta42. The role of perivascular fluid movement and its relationship with CSF biomarkers will require further investigation.

scholarly journals Blood brain barrier leakage is not a consistent feature of white matter lesions in CADASIL

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Rikesh M. Rajani ◽  
Julien Ratelade ◽  
Valérie Domenga-Denier ◽  
Yoshiki Hase ◽  
Hannu Kalimo ◽  
...  
Keyword(s):  
White Matter ◽  
Blood Brain Barrier ◽  
Small Vessel Disease ◽  
White Matter Lesions ◽  
Brain Barrier ◽  
Perivascular Spaces ◽  
Pericyte Coverage ◽  
Blood Brain ◽  
Post Mortem Brain ◽  
Pericyte Loss

AbstractCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic paradigm of small vessel disease (SVD) caused by NOTCH3 mutations that stereotypically lead to the vascular accumulation of NOTCH3 around smooth muscle cells and pericytes. White matter (WM) lesions (WMLs) are the earliest and most frequent abnormalities, and can be associated with lacunar infarcts and enlarged perivascular spaces (ePVS). The prevailing view is that blood brain barrier (BBB) leakage, possibly mediated by pericyte deficiency, plays a pivotal role in the formation of WMLs. Herein, we investigated the involvement of BBB leakage and pericyte loss in CADASIL WMLs. Using post-mortem brain tissue from 12 CADASIL patients and 10 age-matched controls, we found that WMLs are heterogeneous, and that BBB leakage reflects the heterogeneity. Specifically, while fibrinogen extravasation was significantly increased in WMLs surrounding ePVS and lacunes, levels of fibrinogen leakage were comparable in WMLs without other pathology (“pure” WMLs) to those seen in the normal appearing WM of patients and controls. In a mouse model of CADASIL, which develops WMLs but no lacunes or ePVS, we detected no extravasation of endogenous fibrinogen, nor of injected small or large tracers in WMLs. Moreover, there was no evidence of pericyte coverage modification in any type of WML in either CADASIL patients or mice. These data together indicate that WMLs in CADASIL encompass distinct classes of WM changes and argue against the prevailing hypothesis that pericyte coverage loss and BBB leakage are the primary drivers of WMLs. Our results also have important implications for the interpretation of studies on the BBB in living patients, which may misinterpret evidence of BBB leakage within WM hyperintensities as suggesting a BBB related mechanism for all WMLs, when in fact this may only apply to a subset of these lesions.

scholarly journals Brain Invasion along Perivascular Spaces by Glioma Cells: Relationship with Blood–Brain Barrier

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 18 ◽  
Author(s):  
Simone Pacioni ◽  
Quintino Giorgio D’Alessandris ◽  
Mariachiara Buccarelli ◽  
Alessandra Boe ◽  
Maurizio Martini ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Blood Brain Barrier ◽  
Glioma Cells ◽  
Brain Barrier ◽  
Perivascular Spaces ◽  
Brain Invasion ◽  
Blood Brain ◽  
Perivascular Invasion ◽  
The Brain

The question whether perivascular glioma cells invading the brain far from the tumor bulk may disrupt the blood–brain barrier (BBB) represents a crucial issue because under this condition tumor cells would be no more protected from the reach of chemotherapeutic drugs. A recent in vivo study that used human xenolines, demonstrated that single glioma cells migrating away from the tumor bulk are sufficient to breach the BBB. Here, we used brain xenografts of patient-derived glioma stem-like cells (GSCs) to show by immunostaining that in spite of massive perivascular invasion, BBB integrity was preserved in the majority of vessels located outside the tumor bulk. Interestingly, the tumor cells that invaded the brain for the longest distances traveled along vessels with retained BBB integrity. In surgical specimens of malignant glioma, the area of brain invasion showed several vessels with preserved BBB that were surrounded by tumor cells. On transmission electron microscopy, the cell inter-junctions and basal lamina of the brain endothelium were preserved even in conditions in which the tumor cells lay adjacently to blood vessels. In conclusion, BBB integrity associates with extensive perivascular invasion of glioma cells.

Conformationally Constrained Peptide Drugs Targeted at the Blood-Brain Barrier

1995 ◽  
Author(s):  
Thomas P. Davis ◽  
Thomas J. Abbruscato ◽  
Elizabeth Brownson ◽  
Victor J. Hruby
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Peptide Drugs ◽  
Conformationally Constrained ◽  
Blood Brain
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