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

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 +1 more·2010·Cellular and Molecular Neurobiology

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
Venue
Cellular and Molecular Neurobiology
Published
2009-08-29
Volume
30
Issue
2
Pages
247-253
ISSN
  • 0272-4340 (ISSN-L)
  • 1573-6830
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
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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