Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The extracellular matrix of the blood-brain barrier: structural and functional roles in health, aging, and Alzheimer's disease.

ABSTRACT: There is increasing interest in defining the location, content, and role of extracellular matrix (ECM) components in brain structure and function during development, aging, injury, and neurodegeneration. Studies in vivo confirm brain ECM has a dynamic composition with constitutive and induced alterations that impact subsequent cell-cell and cell-matrix interactions. Moreover, it is clear that for any given ECM component, the brain region, and cell type within that location, determines the direction, magnitude, and composition of those changes. This review will examine the ECM at the neurovascular unit (NVU) and the blood-brain barrier (BBB) within the NVU. The discussion will begin at the glycocalyx ECM on the luminal surface of the vasculature, and progress to the abluminal side with a focus on changes in basement membrane ECM during aging and neurodegeneration.

SUBMITTER: Reed MJ

PROVIDER: S-EPMC6866683 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

The extracellular matrix of the blood-brain barrier: structural and functional roles in health, aging, and Alzheimer's disease.

Reed May J MJ Damodarasamy Mamatha M Banks William A WA

Tissue barriers 20190911 4

There is increasing interest in defining the location, content, and role of extracellular matrix (ECM) components in brain structure and function during development, aging, injury, and neurodegeneration. Studies in vivo confirm brain ECM has a dynamic composition with constitutive and induced alterations that impact subsequent cell-cell and cell-matrix interactions. Moreover, it is clear that for any given ECM component, the brain region, and cell type within that location, determines the direct ...[more]

PMID: 31505997

Similar Datasets

Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids

Project description:We established a platform for the brain organoid culture by using human decellularized brain extracellular matrix (BEM) and a microfluidic device. This engineering concept of reconstituting brain-mimetic microenvironments facilitates development of a reliable culture platform for brain organoids, enabling effective modeling and drug development.

2021-06-01 | GSE145386 | GEO

Extracellular vesicles of the blood-brain barrier.

Project description:Extracellular vesicles (ECV), like exosomes, gained recently a lot of attention as potentially playing a significant role in neurodegenerative diseases, particularly in Aβ pathology. While there are a lot of reports on ECV/exosomes derived from a variety of cell types, there is limited information on ECV/exosomes originated from brain microvascular endothelial cells forming the blood-brain barrier (BBB). In this review, we summarize the literature data on brain endothelial ECV/exosomes and present our own data on BBB-derived ECV and their possible involvement in the brain's Aβ pathology. We propose that ECV/exosome release from brain endothelial cells associated with Aβ affects different cells of the neurovascular unit and may be an important contributor to the Aβ deposition in the central nervous system.

| S-EPMC4836554 | biostudies-other

Effects of aging on blood brain barrier and matrix metalloproteases following controlled cortical impact in mice.

Project description:Aging alters the ability of the brain to respond to injury. One of the major differences between the adult and aged brain is that comparable injuries lead to greater blood brain barrier disruption in the aged brain. The goals of these studies were to quantify the effects of age on BBB permeability using high field strength MRI T1 mapping and to determine whether activation of matrix metalloproteases, their inhibitors, or expression of blood brain barrier structural proteins, occludin, zonnula occludins-1 (ZO-1) and claudin-5 were altered following injury to the aged C57/BL6 mouse brain. T1 mapping studies revealed greater blood brain barrier permeability in the aged (21-24 months old) brain than in the adult (4-6 months old) following controlled cortical impact. The increased blood brain barrier permeability in the pericontusional region was confirmed with IgG immunohistochemistry. MMP-9 activity was increased following controlled cortical impact in the aged brain, and this was accompanied by increased MMP-9 gene expression. MMP-2 activity was higher in the uninjured aged brain than in the adult brain. Occludin and ZO-1 mRNA levels were unchanged following injury in either age group, but claudin-5 mRNA levels were lower in the aged than the adult brain following injury. These results demonstrate quantitative increases in blood brain barrier permeability in the aged brain following injury that are accompanied by increased MMP-9 activation and decreased blood brain barrier repair responses.

| S-EPMC4042317 | biostudies-literature

Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids.

Project description:Brain organoids derived from human pluripotent stem cells provide a highly valuable in vitro model to recapitulate human brain development and neurological diseases. However, the current systems for brain organoid culture require further improvement for the reliable production of high-quality organoids. Here, we demonstrate two engineering elements to improve human brain organoid culture, (1) a human brain extracellular matrix to provide brain-specific cues and (2) a microfluidic device with periodic flow to improve the survival and reduce the variability of organoids. A three-dimensional culture modified with brain extracellular matrix significantly enhanced neurogenesis in developing brain organoids from human induced pluripotent stem cells. Cortical layer development, volumetric augmentation, and electrophysiological function of human brain organoids were further improved in a reproducible manner by dynamic culture in microfluidic chamber devices. Our engineering concept of reconstituting brain-mimetic microenvironments facilitates the development of a reliable culture platform for brain organoids, enabling effective modeling and drug development for human brain diseases.

| S-EPMC8342542 | biostudies-literature

Degradation of Extracellular Matrix by Matrix Metalloproteinase 2 Is Essential for the Establishment of the Blood-Brain Barrier in Drosophila.

Project description:The blood-brain barrier (BBB) is an essential system that isolates the central nervous system from the internal environment. Increasing evidence has begun to reveal the molecules that are required for BBB integrity. However, how these components are regulated remains unclear. Here we report that a matrix metalloproteinase, Mmp2, is essential for the establishment of the BBB in Drosophila. In the absence of mmp2, the BBB becomes leaky, which allows the tracer to penetrate the brain. Moreover, the expression pattern of a junctional component, Neuroglian, is altered. We also find that the regulation of the amounts of particular extracellular matrix components is critical for BBB establishment. Furthermore, the process of mesenchymal-epithelial transition of BBB-forming cells is perturbed in the absence of Mmp2. These data indicate that the presence of Mmp(s), which is typically considered to be a risk factor for BBB degradation, is essential for BBB integrity in Drosophila.

| S-EPMC6562144 | biostudies-literature

Blood-brain barrier breakdown in the aging human hippocampus.

Project description:UNLABELLED:The blood-brain barrier (BBB) limits entry of blood-derived products, pathogens, and cells into the brain that is essential for normal neuronal functioning and information processing. Post-mortem tissue analysis indicates BBB damage in Alzheimer's disease (AD). The timing of BBB breakdown remains, however, elusive. Using an advanced dynamic contrast-enhanced MRI protocol with high spatial and temporal resolutions to quantify regional BBB permeability in the living human brain, we show an age-dependent BBB breakdown in the hippocampus, a region critical for learning and memory that is affected early in AD. The BBB breakdown in the hippocampus and its CA1 and dentate gyrus subdivisions worsened with mild cognitive impairment that correlated with injury to BBB-associated pericytes, as shown by the cerebrospinal fluid analysis. Our data suggest that BBB breakdown is an early event in the aging human brain that begins in the hippocampus and may contribute to cognitive impairment. VIDEO ABSTRACT:

| S-EPMC4350773 | biostudies-literature

Bilateral carotid artery stenosis causes unexpected early changes in brain extracellular matrix and blood-brain barrier integrity in mice.

Project description:Bilateral carotid artery stenosis (BCAS) is one experimental model of vascular dementia thought to preferentially impact brain white matter. Indeed, few studies report hippocampal and cortical pathology prior to 30 days post-stenosis; though it is unclear whether those studies examined regions outside the white matter. Since changes in the blood-brain barrier (BBB) permeability precede more overt brain pathology in various diseases, we hypothesized that changes within the BBB and/or BBB-associated extracellular matrix (ECM) could occur earlier after BCAS in the hippocampus, cortex and striatum and be a precursor of longer term pathology. Here, C57Bl/6 mice underwent BCAS or sham surgeries and changes in the BBB and ECM were analyzed by collagen IV (vascular basement membrane component), ?5 integrin (marker of endothelial activation), claudin-5 and occludin (tight junction proteins), Evans blue (permeability marker), Ki-67 (cell proliferation marker), and GFAP and CD11b (glial cell markers) immunohistochemistry after 14 days. Significant changes in markers of cerebrovascular integrity and glial activation were detected, not only in the striatum, but also in the hippocampus and cortex. In conclusion, this study demonstrates for the first time that changes in the BBB/ECM occur shortly after BCAS and within multiple brain regions and suggests such changes might underlie the gradual development of BCAS non-white matter pathology.

| S-EPMC5897017 | biostudies-other

Bilateral carotid artery stenosis causes unexpected early changes in brain extracellular matrix and blood-brain barrier integrity in mice

Project description: Not available

| S-BSST130 | biostudies-other

Alzheimer's disease: A matter of blood-brain barrier dysfunction?

Project description:The blood-brain barrier (BBB) keeps neurotoxic plasma-derived components, cells, and pathogens out of the brain. An early BBB breakdown and/or dysfunction have been shown in Alzheimer's disease (AD) before dementia, neurodegeneration and/or brain atrophy occur. However, the role of BBB breakdown in neurodegenerative disorders is still not fully understood. Here, we examine BBB breakdown in animal models frequently used to study the pathophysiology of AD, including transgenic mice expressing human amyloid-? precursor protein, presenilin 1, and tau mutations, and apolipoprotein E, the strongest genetic risk factor for AD. We discuss the role of BBB breakdown and dysfunction in neurodegenerative process, pitfalls in BBB measurements, and how targeting the BBB can influence the course of neurological disorder. Finally, we comment on future approaches and models to better define, at the cellular and molecular level, the underlying mechanisms between BBB breakdown and neurodegeneration as a basis for developing new therapies for BBB repair to control neurodegeneration.

| S-EPMC5679168 | biostudies-literature

Treatment of Alzheimer's Disease and Blood-Brain Barrier Drug Delivery.

Project description:Despite the enormity of the societal and health burdens caused by Alzheimer's disease (AD), there have been no FDA approvals for new therapeutics for AD since 2003. This profound lack of progress in treatment of AD is due to dual problems, both related to the blood-brain barrier (BBB). First, 98% of small molecule drugs do not cross the BBB, and ~100% of biologic drugs do not cross the BBB, so BBB drug delivery technology is needed in AD drug development. Second, the pharmaceutical industry has not developed BBB drug delivery technology, which would enable industry to invent new therapeutics for AD that actually penetrate into brain parenchyma from blood. In 2020, less than 1% of all AD drug development projects use a BBB drug delivery technology. The pathogenesis of AD involves chronic neuro-inflammation, the progressive deposition of insoluble amyloid-beta or tau aggregates, and neural degeneration. New drugs that both attack these multiple sites in AD, and that have been coupled with BBB drug delivery technology, can lead to new and effective treatments of this serious disorder.

| S-EPMC7697739 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data