Pericytes from brain microvessels strengthen the barrier integrity in primary cultures of rat brain endothelial cells

Shinsuke Nakagawa, M. Deli, Shinobu Nakao, Masaru Honda, Kentaro Hayashi, Ryota Nakaoke, Yasufumi Kataoka, Masami Niwa

Research output: Contribution to journalArticle

226 Citations (Scopus)

Abstract

(1) The blood-brain barrier (BBB) characteristics of cerebral endothelial cells are induced by organ-specific local signals. Brain endothelial cells lose their phenotype in cultures without cross-talk with neighboring cells. (2) In contrast to astrocytes, pericytes, another neighboring cell of endothelial cells in brain capillaries, are rarely used in BBB co-culture systems. (3) Seven different types of BBB models, mono-culture, double and triple co-cultures, were constructed from primary rat brain endothelial cells, astrocytes and pericytes on culture inserts. The barrier integrity of the models were compared by measurement of transendothelial electrical resistance and permeability for the small molecular weight marker fluorescein. (4) We could confirm that brain endothelial monolayers in mono-culture do not form tight barrier. Pericytes induced higher electrical resistance and lower permeability for fluorescein than type I astrocytes in co-culture conditions. In triple co-culture models the tightest barrier was observed when endothelial cells and pericytes were positioned on the two sides of the porous filter membrane of the inserts and astrocytes at the bottom of the culture dish. (5) For the first time a rat primary culture based syngeneic triple co-culture BBB model has been constructed using brain pericytes beside brain endothelial cells and astrocytes. This model, mimicking closely the anatomical position of the cells at the BBB in vivo, was superior to the other BBB models tested. (6) The influence of pericytes on the BBB properties of brain endothelial cells may be as important as that of astrocytes and could be exploited in the construction of better BBB models.

Original languageEnglish
Pages (from-to)687-694
Number of pages8
JournalCellular and Molecular Neurobiology
Volume27
Issue number6
DOIs
Publication statusPublished - Sep 2007

Fingerprint

Pericytes
Endothelial cells
Microvessels
Blood-Brain Barrier
Cell culture
Rats
Brain
Endothelial Cells
Astrocytes
Coculture Techniques
Acoustic impedance
Fluorescein
Electric Impedance
Permeability
Die casting inserts
Monolayers
Molecular Weight
Molecular weight
Membranes
Phenotype

Keywords

  • Astrocytes
  • Blood-brain barrier
  • Brain endothelial cells
  • Co-culture
  • In vitro BBB model (rat)
  • Pericytes
  • Permeability
  • Transendothelial electrical resistance

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Biochemistry
  • Cell Biology
  • Genetics

Cite this

Pericytes from brain microvessels strengthen the barrier integrity in primary cultures of rat brain endothelial cells. / Nakagawa, Shinsuke; Deli, M.; Nakao, Shinobu; Honda, Masaru; Hayashi, Kentaro; Nakaoke, Ryota; Kataoka, Yasufumi; Niwa, Masami.

In: Cellular and Molecular Neurobiology, Vol. 27, No. 6, 09.2007, p. 687-694.

Research output: Contribution to journalArticle

Nakagawa, Shinsuke ; Deli, M. ; Nakao, Shinobu ; Honda, Masaru ; Hayashi, Kentaro ; Nakaoke, Ryota ; Kataoka, Yasufumi ; Niwa, Masami. / Pericytes from brain microvessels strengthen the barrier integrity in primary cultures of rat brain endothelial cells. In: Cellular and Molecular Neurobiology. 2007 ; Vol. 27, No. 6. pp. 687-694.
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