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Pyroptosis, BBB disruption, bacterial meningitis, endothelial cell, microglia

ABSTRACT: Blood-brain barrier (BBB) is a highly specialized membrane that maintains brain homeostasis. The breakdown of the BBB is associated with various neuro-inflammatory diseases. The mechanisms of inflammatory BBB disruption and inflammation transmission in the neuroinflammatory microenvironment remain largely unknown. Here, we showed that brain endothelial cells (ECs) prominently responded to neonatal meningitis Escherichia coli (NMEC) challenge and underwent GSDMD-dependent pyroptosis. By using spatialtemporal single-cell transcriptomic sequencing and proteomics sequencing of mouse brain after NMEC infection, we found that Gbp5 was required for brain EC pyroptosis during inflammatory BBB disruption. Furthermore, we identified a homeostasis-inflammation state transition both in EC and microglia (MG) during pyroptosis. Pyroptotic EC can induce MG pyroptosis via Angptl4-Sdc4 signaling. This interaction leads to a model of “pyroptosis cascade” between brain EC and MG in the central nervous system (CNS). The EC-MG py

ORGANISM(S): Mus Musculus

SUBMITTER: Haiqing Xiong

PROVIDER: PXD072742 | iProX | Wed Jan 07 00:00:00 GMT 2026

REPOSITORIES: iProX

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Transcriptomic analysis in cerebral microvessels from the brain of endothelial-specific Crif1 deficiency mouse

Project description:Endothelial cells (ECs) in cerebral vessels are considered the primary targets in acute hemorrhagic brain injuries. EC dysfunction can aggravate neuronal injuries by causing secondary inflammatory responses and blood-brain barrier (BBB) disruption. ECs comprising the BBB are known to have a higher mitochondrial volume compared with peripheral ECs. In previous study, we reported Tek-CRIF1-knockout (KO) mice, with EC-specific deletion of the mitochondrial OxPhos-related gene, Crif1, also known as Gadd45gip1 (encoding GADD45G-interacting protein 1), display profound BBB defects accompanied by reduced expression of junctional proteins in ECs. To identify signaling pathways involved in linking EC-specific mitochondrial dysfunction and BBB disruption, we first performed RNA sequencing using isolated cerebral vessels from Tek-CRIF1 mice. This transcriptome analyses of the Tek-CRIF1-KO mouse revealed significant changes in some signaling, a pathway intimately involved in BBB maintenance.

2022-08-31 | GSE207106 | GEO

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Brain endothelial GSDMD activation mediates inflammatory BBB breakdown

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Microglial NLRP3-gasdermin D activation impairs blood-brain barrier integrity through interleukin-1β-independent neutrophil chemotaxis upon peripheral inflammation

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Vascular endothelial S1PR2 aggravates cardiac ischemia/reperfusion injury through triggering mitochondrial dysfunctions and endothelial pyroptosis via RHO/ROCK1/DRP1/NLRP3 pathway [endothelial cells]

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Vascular endothelial S1PR2 aggravates cardiac ischemia/reperfusion injury through triggering mitochondrial dysfunctions and endothelial pyroptosis via RHO/ROCK1/DRP1/NLRP3 pathway [heart]

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Comparative genomic hybridization by array of rat brain- and spinal cord-derived microvascular endothelial cells, in basal and inflammatory conditions upon different time points of TNF-Î±-treatment or TWEAK-treatment or LPS-treatment.

Project description:The brain and spinal cord are endowed with particular vascular systems, known as the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) respectively, which maintain homeostasis between nervous parenchyma and peripheral circulation. Despite these common features, the BSCB presents structural and functional differences resulting in distinct vulnerability to pathological insults when compared to the BBB. Although, the heterogeneity of endothelial cell types underlies their remarkable ability to sub-specialize and provide specific requirements for a given vascular bed, very little is known concerning intrinsic differences between microvascular endothelial cells (MECs) derived from brain (BMECs) and spinal cord (SCMECs), including their response to inflammation. We used Agilent Whole Rattus Genome Microarray 4X44K to compare rat BMECs and SCMECs in both basal and inflammatory conditions; TNF-Î±-induced, TWEAK-induced and LPS-induced gene expression after 6 hr, 12 hr, 24 hr and 48 hr incubation.

2016-06-20 | E-MTAB-4696 | biostudies-arrayexpress

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Project description:Electronic cigarette (EC) use has grown substantially since entry into the US market, particularly among adolescents and combustible tobacco users. Despite growing popularity and claims of harm reduction, the health effects of these products outside the lung is poorly understood. Several constituents of cigarette smoke (CS) with known neurovascular and inflammatory effects are present in EC liquids or formed during the generation of vapor. The present study characterizes the impact of EC exposure on neuroinflammation and blood-brain barrier (BBB) function, and provides comparison of outcomes with reference cigarette exposure normalized to comparable levels of nicotine delivery. Additionally, the contribution of nicotine to observed effects is elucidated through comparison with EC liquids which are verified to be nicotine-free. C57BL/6 mice are exposed to 2 hrs of daily EC vapor or CS, beginning at 8 wks of age. Changes in BBB gene expression are first characterized by whole exome sequencing of isolated brain microvessels following chronic (2 month) EC exposure.

2020-11-23 | GSE142400 | GEO

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