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Human neurovascular unit chip with a functional blood-brain barrier models brain-infection mechanism of a fungal meningitis pathogen

ABSTRACT: Human neurovascular unit chip with a functional blood-brain barrier models brain-infection mechanism of a fungal meningitis pathogen

PROVIDER: PRJNA721424 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14215370_1.fastq.gz	Fastqsanger.gz
	SRR14215370_2.fastq.gz	Fastqsanger.gz
	SRR14215371_1.fastq.gz	Fastqsanger.gz
	SRR14215371_2.fastq.gz	Fastqsanger.gz

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Human neurovascular unit chip with a functional blood-brain barrier models brain-infection mechanism of a fungal meningitis pathogen

Project description:Reconstitution of a neurovascular unit model with blood-brain barrier (BBB) function is of great importance for drug development targeting cerebral diseases and study of brain disease mechanisms. In this study, we describe a human neurovascular unit chip designed by reconstituting necessary cellular and extracellular components in microfluidic devices. Dynamic three-dimensional co-culture of human cells (neural stem cells, brain microvascular endothelial cells, and brain vascular pericytes) in microfluidics with a stepwise unidirectional flow successfully established the chip with BBB-mimetic structural and functional features to be an effective barrier for drugs and cytokines. Furthermore, we showed the utility of the chip by modeling the neurotropic behaviors and BBB penetration process of a global fungal meningitis pathogen, Cryptococcus neoformans. This chip is the first in vitro experimental model for monitoring neurotropism of C. neoformans and would contribute to the investigation of various cerebral disorders, including microbial infectious diseases and their corresponding drug development.

2021-04-13 | GSE171937 | GEO

Type 2 Diabetes Mellitus is Associated with Transcriptome Alterations in Cortical Neurones and Associated Neurovascular Unit Cells in the Ageing Brain

Project description:Type 2 diabetes mellitus (T2D), characterised by peripheral insulin resistance, is a risk factor for dementia. In addition to its contribution to small and large vessel disease, T2D may directly damage cells of the brain neurovascular unit. In this study, we investigated the transcriptomic changes in cortical neurones, and associated astrocytes and endothelial cells of the neurovascular unit, in the ageing brain

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A microfluidic chip recapitulating the human neurovascular unit with a functional blood-brain barrier for modeling gut-brain interactions

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The endfeetome, a astroglial translatome of the neurovascular unit

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Project description:The neurovascular unit, which includes neurons, glial cells, and vascular cells, plays crucial roles in the onset and progression of Alzheimer’s disease (AD). Therefore, effective drugs against AD should be able to target the multi-cellular neurovascular unit and the therapeutic relationships among neurovascular cells should be defined. We aimed to examine the therapeutic effects of an herbal remedy with multi-targeting capabilities, ukgansan (UGS), using in vitro models of AD, and to assess the similarity among neurovascular cells in terms of a therapeutic network.

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Project description:Cerebral small vessel disease (SVD) is frequently comorbid with Alzheimer’s disease (AD) and vascular brain endothelial cells (BECs) are enriched for the expression of genes associated with AD genetic risk. However, the gene regulatory landscapes of neurovascular cells and their intersection with genetic risk for disease remains unexplored. Here we have generated gene regulomes for human BECs, mural cells and other brain cell types to show that AD heritability is primarily immune-related and that it shows modest enrichment in BECs. By contrast, genetic risk for SVD is enriched across cells of the neurovascular unit, including astrocytes. Enhancer-to-gene interactomes implicate amyloid processes in both AD and SVD, though the risk genes are mostly distinct for the two disorders. Motifs for putative partners of lineage transcription factors in microglia and BECs were enriched for AD and SVD variants at genes linked to disease pathways. Gene prioritization and enrichment analyses further identified potential repurposable drugs for AD. Our findings highlight novel regulatory mechanisms and therapeutic targets within the neurovascular system.

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