Neutrophil-derived microvesicle induced dysfunction of the blood-brain barrier in vitro
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE137111 | GEO | 2019/12/05
REPOSITORIES: GEO
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Project description:Functional and structural dysfunction of the blood brain barrier (BBB) leads to severe alterations in brain physiology and is believed to trigger neurodegeneration. To investigate the molecular mechanisms driving the BBB dysfunction, very few human BBB cell culture models are available; of which, the human microvascular endothelial cell line (hCMEC/D3) is the most widely used. Thus far, array-based approaches or targeted seqeuncing based approaches have been employed to characterize the gene expression of the hCMEC/D3 model. However,The goal of this study is to perform deep transcriptomic sequencing of the BBB cell line and obtain features like gene expression, expressed single nucleotide variants, alternate splice forms, circular RNAs, long non-coding RNAs and micro RNAs. We have developed blood brain barriers transcriptomics landscape using RNA sequencing and micro RNA seqeuncing data obtained from replicates of hCMEC/D3 BBB cell line.
2016-03-17 | E-GEOD-76528 | biostudies-arrayexpress
Project description:Functional and structural dysfunction of the blood brain barrier (BBB) leads to severe alterations in brain physiology and is believed to trigger neurodegeneration. To investigate the molecular mechanisms driving the BBB dysfunction, very few human BBB cell culture models are available;of which, the human microvascular endothelial cell line (hCMEC/D3) is the most widely used. Thus far, array-based approaches or targeted seqeuncing based approaches have been employed to characterize the gene expression of the hCMEC/D3 model. However,The goal of this study is to perform deep transcriptomic sequencing of the BBB cell line and obtain features like gene expression, expressed single nucleotide variants, alternate splice forms, circular RNAs, long non-coding RNAs and micro RNAs. We have developed blood brain barriers transcriptomics landscape using RNA and micro RNA sequencing data obtained from replicates of hCMEC/D3 BBB cell line.
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Project description:The human immortalized brain endothelial cell line hCMEC/D3 is considered an in vitro model of the blood-brain-barrier. We aimed to characterize changes in the secretome of hCMEC/D3 subjected to oxygen and glucose deprivation (OGD) by SILAC, in order to identify new proteins involved in ischemia-triggered blood-brain-barrier disruption and test their potential as blood biomarkers for ischemic stroke diagnosis. After SILAC analysis, 19 proteins were found differentially secreted between OGD and normoxia/normoglycemia conditions (Fold Change>|1.4| and peptide count≥2). Protein folding and nucleic acid binding were the main molecular functions and epithelial adherens junctions and aldosterone signaling appeared as the main canonical pathways represented by OGD-secreted proteins. ANXA1, CLUS, IGFBP2, PRDX3, TIMP2 and COL1A2 were replicated by western blotting in 9 independent cell cultures. Five replicated proteins were analyzed in human serum samples of 38 ischemic stroke patients compared to 18 stroke-mimicking conditions and 18 healthy controls by ELISA. IGFBP2 showed increased blood levels when strokes were compared with stroke-mimicking patients (p<0.1). In conclusion, we characterized changes in the secretome of hCMEC/D3 after an ischemic insult and highlighted some candidates to become biomarkers for ischemic stroke diagnosis related to blood-brain-barrier disruption.
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2022-08-12 | PXD030493 | Pride
Project description:Qosa2014 - Mechanistic modeling that
describes Aβ clearance across BBB
Qosa2014 - Mechanistic modeling that
describes Aβ clearance across BBB.
Encoded non-curated model. Issues:
- Confusing equation 6
- Missing initial values for spices
This model is described in the article:
Differences in amyloid-?
clearance across mouse and human blood-brain barrier models:
kinetic analysis and mechanistic modeling.
Qosa H, Abuasal BS, Romero IA,
Weksler B, Couraud PO, Keller JN, Kaddoumi A.
Neuropharmacology 2014 Apr; 79:
668-678
Abstract:
Alzheimer's disease (AD) has a characteristic hallmark of
amyloid-? (A?) accumulation in the brain. This accumulation of
A? has been related to its faulty cerebral clearance. Indeed,
preclinical studies that used mice to investigate A? clearance
showed that efflux across blood-brain barrier (BBB) and brain
degradation mediate efficient A? clearance. However, the
contribution of each process to A? clearance remains unclear.
Moreover, it is still uncertain how species differences between
mouse and human could affect A? clearance. Here, a modified
form of the brain efflux index method was used to estimate the
contribution of BBB and brain degradation to A? clearance from
the brain of wild type mice. We estimated that 62% of
intracerebrally injected (125)I-A?40 is cleared across BBB
while 38% is cleared by brain degradation. Furthermore,
in vitro and in silico studies were performed to compare
A? clearance between mouse and human BBB models. Kinetic
studies for A?40 disposition in bEnd3 and hCMEC/D3 cells,
representative in vitro mouse and human BBB models,
respectively, demonstrated 30-fold higher rate of (125)I-A?40
uptake and 15-fold higher rate of degradation by bEnd3 compared
to hCMEC/D3 cells. Expression studies showed both cells to
express different levels of P-glycoprotein and RAGE, while LRP1
levels were comparable. Finally, we established a mechanistic
model, which could successfully predict cellular levels of
(125)I-A?40 and the rate of each process. Established
mechanistic model suggested significantly higher rates of A?
uptake and degradation in bEnd3 cells as rationale for the
observed differences in (125)I-A?40 disposition between mouse
and human BBB models. In conclusion, current study demonstrates
the important role of BBB in the clearance of A? from the
brain. Moreover, it provides insight into the differences
between mouse and human BBB with regards to A? clearance and
offer, for the first time, a mathematical model that describes
A? clearance across BBB.
This model is hosted on
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and identified by:
MODEL1409240002.
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2015-04-15 | MODEL1409240002 | BioModels
Project description:Functional and structural dysfunction of the blood brain barrier (BBB) leads to severe alterations in brain physiology and is believed to trigger neurodegeneration. To investigate the molecular mechanisms driving the BBB dysfunction, very few human BBB cell culture models are available;of which, the human microvascular endothelial cell line (hCMEC/D3) is the most widely used. Thus far, array-based approaches or targeted seqeuncing based approaches have been employed to characterize the gene expression of the hCMEC/D3 model. However,The goal of this study is to perform deep transcriptomic sequencing of the BBB cell line and obtain features like gene expression, expressed single nucleotide variants, alternate splice forms, circular RNAs, long non-coding RNAs and micro RNAs.
2016-03-17 | GSE76530 | GEO