Dual microglia effects on blood brain barrier permeability induced by systemic inflammation

Koichiro Haruwaka, Ako Ikegami, Yoshihisa Tachibana, Nobuhiko Ohno, Hiroyuki Konishi, Akari Hashimoto, Mami Matsumoto, Daisuke Kato, Riho Ono, Hiroshi Kiyama, Andrew J. Moorhouse, Junichi Nabekura and Hiroaki Wake ()
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Koichiro Haruwaka: Kobe University Graduate School of Medicine
Ako Ikegami: Kobe University Graduate School of Medicine
Yoshihisa Tachibana: Kobe University Graduate School of Medicine
Nobuhiko Ohno: Jichi Medical University
Hiroyuki Konishi: Nagoya University Graduate School of Medicine
Akari Hashimoto: Kobe University Graduate School of Medicine
Mami Matsumoto: National Institute for Physiological Sciences
Daisuke Kato: Kobe University Graduate School of Medicine
Riho Ono: Kobe University Graduate School of Medicine
Hiroshi Kiyama: Nagoya University Graduate School of Medicine
Andrew J. Moorhouse: The University of New South Wales
Junichi Nabekura: National Institutes of Natural Sciences
Hiroaki Wake: Kobe University Graduate School of Medicine

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-13812-z

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