Cited by 179Barrier Structure and Function StudiesNeuroinflammation and Neurodegeneration MechanismsExtracellular vesicles in disease

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Lipopolysaccharide-activated microglia induce dysfunction of the blood-brain barrier in rat microvascular endothelial cells co-cultured with microglia

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Sumi, Noriko, Nishioku, Tsuyoshi, Takata, Fuyuko, Matsumoto, Junichi, Watanabe, Takuya, Shuto, Hideki, Yamauchi, Atsushi, Dohgu, Shinya, Kataoka, Yasufumi·2010·Cellular and Molecular Neurobiology

DOI 10.1007/s10571-009-9446-7PMC PMC11498813

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Abstract

The blood-brain barrier (BBB) is formed by brain capillary endothelial cells, astrocytes, pericytes, microglia, and neurons. BBB disruption under pathological conditions such as neurodegenerative disease and inflammation is observed in parallel with microglial activation. To test whether activation of microglia is linked to BBB dysfunction, we evaluated the effect of lipopolysaccharide (LPS) on BBB functions in an in vitro co-culture system with rat brain microvascular endothelial cells (RBEC) and microglia. When LPS was added for 6 h to the abluminal side of RBEC/microglia co-culture at a concentration showing no effects on the RBEC monolayer, transendothelial electrical resistance was decreased and permeability to sodium-fluorescein was increased in RBEC. Immunofluorescence staining for tight junction proteins demonstrated that zonula occludens-1-, claudin-5-, and occludin-like immunoreactivities at the intercellular borders of RBEC were fragmented in the presence of LPS-activated microglia. These functional changes induced by LPS-activated microglia were blocked by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, diphenyleneiodonium chloride. The present findings suggest that LPS activates microglia to induce dysfunction of the BBB by producing reactive oxygen species through NADPH oxidase.

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Authors: Sumi, N., Nishioku, T., Takata, F., Matsumoto, J., Watanabe, T., Shuto, H., Yamauchi, A., Dohgu, S., & Kataoka, Y.
Affiliations: Fukuoka University (JP)
Corresponding author: Kataoka, Yasufumi
ORCID: Nishioku, Tsuyoshi
Takata, Fuyuko
Matsumoto, Junichi
Watanabe, Takuya
Yamauchi, Atsushi
Dohgu, Shinya
Venue: Cellular and Molecular Neurobiology
Publisher: Springer Science and Business Media LLC
Published: 2009-08-29
Volume: 30
Issue: 2
Pages: 247-253
ISSN: 0272-4340 (ISSN-L)
1573-6830
DOI: 10.1007/s10571-009-9446-7
PMC: PMC11498813
OpenAlex: W1990985572
Cited by: 179
References: 33
Citations by year: 2026: 6 · 2025: 8 · 2024: 16 · 2023: 11 · 2022: 13 · 2021: 20 · 2020: 14 · 2019: 13 · 2018: 14 · 2017: 12 · 2016: 12 · 2015: 11 · 2014: 8 · 2013: 5 · 2012: 5
FWCI: 3.41
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Cellular and Molecular Neurobiology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Keywords: blood-brain barrier dysfunction, microglial activation, lipopolysaccharide, brain microvascular endothelial cells, endothelial permeability, tight junction proteins, zonula occludens-1, claudin-5, occludin, NADPH oxidase, reactive oxygen species, diphenyleneiodonium, transendothelial electrical resistance, co-culture model
MeSH terms: Animals, Blood-Brain Barrier, Cell Membrane Permeability, Lipopolysaccharides, Rats, Wistar, Reactive Oxygen Species, Microglia, Coculture Techniques, Endothelial Cells, Rats

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Lipopolysaccharide-activated microglia induce dysfunction of the blood-brain barrier in rat microvascular endothelial cells co-cultured with microglia

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