Abstract

Microglia survey brain parenchyma, responding to injury and infections. Microglia also respond to systemic disease, but the role of blood–brain barrier (BBB) integrity in this process remains unclear. Using simultaneous in vivo imaging, we demonstrated that systemic inflammation induces CCR5-dependent migration of brain resident microglia to the cerebral vasculature. Vessel-associated microglia initially maintain BBB integrity via expression of the tight-junction protein Claudin-5 and make physical contact with endothelial cells. During sustained inflammation, microglia phagocytose astrocytic end-feet and impair BBB function. Our results show microglia play a dual role in maintaining BBB integrity with implications for elucidating how systemic immune-activation impacts neural functions.

Details

Title
Dual microglia effects on blood brain barrier permeability induced by systemic inflammation
Author
Haruwaka, Koichiro 1 ; Ikegami, Ako 2 ; Tachibana, Yoshihisa 2   VIAFID ORCID Logo  ; Ohno, Nobuhiko 3 ; Konishi, Hiroyuki 4 ; Hashimoto, Akari 2   VIAFID ORCID Logo  ; Matsumoto, Mami 5 ; Kato, Daisuke 6 ; Ono, Riho 2 ; Kiyama, Hiroshi 4   VIAFID ORCID Logo  ; Moorhouse, Andrew J 7   VIAFID ORCID Logo  ; Nabekura, Junichi 8 ; Wake, Hiroaki 9   VIAFID ORCID Logo 

1  Division of System Neuroscience, Kobe University Graduate School of Medicine, Kobe, Japan; Division of Homeostatic Development, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan; Department of Physiological Sciences, The Graduate School for Advanced Study, Hayama, Japan 
2  Division of System Neuroscience, Kobe University Graduate School of Medicine, Kobe, Japan 
3  Department of Anatomy, Division of Histology and Cell Biology, Jichi Medical University, Tochigi, Japan; Division of Ultrastructural Research, National Institute for Physiological Sciences, Okazaki, Japan 
4  Department of Functional Anatomy and Neuroscience, Nagoya University Graduate School of Medicine, Nagoya, Japan 
5  Section of Electron Microscopy, Supportive Center for Brain Research, National Institute for Physiological Sciences, Okazaki, Japan; Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan 
6  Division of System Neuroscience, Kobe University Graduate School of Medicine, Kobe, Japan; Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan 
7  School of Medical Sciences, The University of New South Wales, Sydney, NSW, Australia 
8  Division of Homeostatic Development, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan; Department of Physiological Sciences, The Graduate School for Advanced Study, Hayama, Japan 
9  Division of System Neuroscience, Kobe University Graduate School of Medicine, Kobe, Japan; Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama, Japan; Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama, Japan 
Pages
1-17
Publication year
2019
Publication date
Dec 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-13812-z
ProQuest document ID
2329323917
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.