Role of microRNAs on Blood Brain Barrier Dysfunction in Vascular Cognitive Impairment

The entry of blood-borne macromolecular substances into the brain parenchyma from cerebral vessels is blocked by the blood–brain barrier (BBB) function. Accordingly, increased permeability of the vessels induced by insult noted in patients suffering from vascular dementia likely contributes to the cognitive impairment. On the other hand, blood-borne substances can enter extracellular spaces of the brain via endothelial cells at specific sites without the BBB, and can move to brain parenchyma, such as the hippocampus and periventricular areas, adjacent to specific sites, indicating the contribution of increased permeability of vessels in the specific sites to brain function. It is necessary to consider influx and efflux of interstitial fluid (ISF) and cerebrospinal fluid (CSF) in considering effects of brain transfer of intravascular substances on brain function. Two pathways of ISF and CSF are recently being established. One is the intramural peri-arterial drainage (IPAD) pathway of ISF. The other is the glymphatic system of CSF. Dysfunction of the two pathways could also contribute to brain dysfunction. We review the effects of several kinds of insult on vascular permeability and the failure of fluid clearance on the brain function.

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Review: Role of developmental inflammation and blood-brain barrier dysfunction in neurodevelopmental and neurodegenerative diseases

Neuropathology and Applied Neurobiology ◽

10.1111/j.1365-2990.2008.01005.x ◽

2009 ◽

Vol 35 (2) ◽

pp. 132-146 ◽

Cited By ~ 130

Author(s):

H. B. Stolp ◽

K. M. Dziegielewska

Keyword(s):

Neurodegenerative Diseases ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Barrier Dysfunction ◽

Blood Brain

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The Dual Role of Microglia in Blood-Brain Barrier Dysfunction after Stroke

Current Neuropharmacology ◽

10.2174/1570159x18666200529150907 ◽

2020 ◽

Vol 18 (12) ◽

pp. 1237-1249 ◽

Cited By ~ 1

Author(s):

Ruiqing Kang ◽

Marcin Gamdzyk ◽

Cameron Lenahan ◽

Jiping Tang ◽

Sheng Tan ◽

...

Keyword(s):

Endothelial Cells ◽

Blood Brain Barrier ◽

Vital Role ◽

Dual Role ◽

Brain Barrier ◽

Barrier Dysfunction ◽

Blood Brain ◽

M2 Microglia ◽

The Brain

It is well-known that stroke is one of the leading causes of death and disability all over the world. After a stroke, the blood-brain barrier subsequently breaks down. The BBB consists of endothelial cells surrounded by astrocytes. Microglia, considered the long-living resident immune cells of the brain, play a vital role in BBB function. M1 microglia worsen BBB disruption, while M2 microglia assist in repairing BBB damage. Microglia can also directly interact with endothelial cells and affect BBB permeability. In this review, we are going to discuss the mechanisms responsible for the dual role of microglia in BBB dysfunction after stroke.

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Role of endothelial TRPA1 expression in blood‐brain barrier dysfunction

Alzheimer s & Dementia ◽

10.1002/alz.058550 ◽

2021 ◽

Vol 17 (S2) ◽

Author(s):

Euitaek Yang ◽

Amal Kaddoumi

Keyword(s):

Blood Brain Barrier ◽

Brain Barrier ◽

Barrier Dysfunction ◽

Blood Brain

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Improvement of autophagy dysfunction as a potential mechanism for environmental enrichment to protect blood-brain barrier in rats with vascular cognitive impairment

Neuroscience Letters ◽

10.1016/j.neulet.2020.135437 ◽

2020 ◽

Vol 739 ◽

pp. 135437

Author(s):

Linling Xu ◽

Changhua Qu ◽

Chujie Qu ◽

Jun Shen ◽

Hao Song ◽

...

Keyword(s):

Cognitive Impairment ◽

Blood Brain Barrier ◽

Environmental Enrichment ◽

Vascular Cognitive Impairment ◽

Brain Barrier ◽

Potential Mechanism ◽

Blood Brain

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The Role of Brain Microvascular Endothelial Cell and Blood-Brain Barrier Dysfunction in Schizophrenia

Complex Psychiatry ◽

10.1159/000511552 ◽

2020 ◽

Vol 6 (1-2) ◽

pp. 30-46

Author(s):

Sovannarath Pong ◽

Rakesh Karmacharya ◽

Marianna Sofman ◽

Jeffrey R. Bishop ◽

Paulo Lizano

Keyword(s):

Blood Brain Barrier ◽

Association Studies ◽

Central Element ◽

Brain Barrier ◽

Microvascular Endothelial Cell ◽

Genome Wide Association Studies ◽

Barrier Dysfunction ◽

Blood Brain ◽

Microvascular Endothelial

Background: Despite decades of research, little clarity exists regarding pathogenic mechanisms related to schizophrenia. Investigations on the disease biology of schizophrenia have primarily focused on neuronal alterations. However, there is substantial evidence pointing to a significant role for the brain’s microvasculature in mediating neuroinflammation in schizophrenia. Summary: Brain microvascular endothelial cells (BMEC) are a central element of the microvasculature that forms the blood-brain barrier (BBB) and shields the brain against toxins and immune cells via paracellular, transcellular, transporter, and extracellular matrix proteins. While evidence for BBB dysfunction exists in brain disorders, including schizophrenia, it is not known if BMEC themselves are functionally compromised and lead to BBB dysfunction. Key Messages: Genome-wide association studies, postmortem investigations, and gene expression analyses have provided some insights into the role of the BBB in schizophrenia pathophysiology. However, there is a significant gap in our understanding of the role that BMEC play in BBB dysfunction. Recent advances differentiating human BMEC from induced pluripotent stem cells (iPSC) provide new avenues to examine the role of BMEC in BBB dysfunction in schizophrenia.

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1958-P: Role of Leptin in Blood-Brain Barrier Dysfunction

Diabetes ◽

10.2337/db19-1958-p ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 1958-P

Author(s):

THERESE S. SALAMEH ◽

WILLIAM MORTELL ◽

WILLIAM A. BANKS

Keyword(s):

Blood Brain Barrier ◽

Brain Barrier ◽

Barrier Dysfunction ◽

Blood Brain

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

Stroke ◽

10.1161/str.47.suppl_1.44 ◽

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.

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