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Cell and Tissue Research

, Volume 363, Issue 2, pp 497–511 | Cite as

Heterogeneous vascular permeability and alternative diffusion barrier in sensory circumventricular organs of adult mouse brain

  • Shoko Morita
  • Eriko Furube
  • Tetsuya Mannari
  • Hiroaki Okuda
  • Kouko Tatsumi
  • Akio Wanaka
  • Seiji MiyataEmail author
Regular Article

Abstract

Fenestrated capillaries of the sensory circumventricular organs (CVOs), including the organum vasculosum of the lamina terminalis, the subfornical organ and the area postrema, lack completeness of the blood–brain barrier (BBB) to sense a variety of blood-derived molecules and to convey the information into other brain regions. We examine the vascular permeability of blood-derived molecules and the expression of tight-junction proteins in sensory CVOs. The present tracer assays revealed that blood-derived dextran 10 k (Dex10k) having a molecular weight (MW) of 10,000 remained in the perivascular space between the inner and outer basement membranes, but fluorescein isothiocyanate (FITC; MW: 389) and Dex3k (MW: 3000) diffused into the parenchyma. The vascular permeability of FITC was higher at central subdivisions than at distal subdivisions. Neither FITC nor Dex3k diffused beyond the dense network of glial fibrillar acidic protein (GFAP)-positive astrocytes/tanycytes. The expression of tight-junction proteins such as occludin, claudin-5 and zonula occludens-1 (ZO-1) was undetectable at the central subdivisions of the sensory CVOs but some was expressed at the distal subdivisions. Electron microscopic observation showed that capillaries were surrounded with numerous layers of astrocyte processes and dendrites. The expression of occludin and ZO-1 was also observed as puncta on GFAP-positive astrocytes/tanycytes of the sensory CVOs. Our study thus demonstrates the heterogeneity of vascular permeability and expression of tight-junction proteins and indicates that the outer basement membrane and dense astrocyte/tanycyte connection are possible alternative mechanisms for a diffusion barrier of blood-derived molecules, instead of the BBB.

Keywords

Blood–brain barrier Tight junction Vascular permeability Astrocyte Perivascular space Mouse 

Notes

Acknowledgments

The hybridomas of anti-PV-1 (MECA-32) IgG developed by Dr. Eugene C Butcher and anti-ZO-1 IgG developed by Dr. Daniel A. Goodenough were obtained from the DSHB, which was developed under the auspices of the National Institute of Child Health and Human Development and is maintained by The University of Iowa, Iowa City, IA 52242, USA.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Shoko Morita
    • 1
    • 2
  • Eriko Furube
    • 1
  • Tetsuya Mannari
    • 1
  • Hiroaki Okuda
    • 2
  • Kouko Tatsumi
    • 2
  • Akio Wanaka
    • 2
  • Seiji Miyata
    • 1
    Email author
  1. 1.Department of Applied BiologyKyoto Institute of TechnologyKyotoJapan
  2. 2.Department of Anatomy and Neuroscience, Faculty of MedicineNara Medical UniversityKashiharaJapan

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