Dual microglia effects on blood brain barrier permeability induced by systemic inflammation.,Nature Communications

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Dual microglia effects on blood brain barrier permeability induced by systemic inflammation.
Nature Communications ( IF 14.7 ) Pub Date : 2019-12-20 , DOI: 10.1038/s41467-019-13812-z
Koichiro Haruwaka _{1,

2,

3} , Ako Ikegami ₁ , Yoshihisa Tachibana ₁ , Nobuhiko Ohno _{4,

5} , Hiroyuki Konishi ₆ , Akari Hashimoto ₁ , Mami Matsumoto _{7,

8} , Daisuke Kato _{1,

9} , Riho Ono ₁ , Hiroshi Kiyama ₆ , Andrew J Moorhouse ₁₀ , Junichi Nabekura _{2,

3} , Hiroaki Wake _{1,

9,

11,

12}

Affiliation

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.
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.
Department of Functional Anatomy and Neuroscience, Nagoya University Graduate School of Medicine, Nagoya, Japan.
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.
Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
School of Medical Sciences, The University of New South Wales, Sydney, NSW, Australia.
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.

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.

中文翻译：

双重小胶质细胞对由全身性炎症引起的血脑屏障通透性的影响。

小胶质细胞调查脑实质，对损伤和感染有反应。小胶质细胞也对全身性疾病有反应，但在此过程中血脑屏障（BBB）完整性的作用仍不清楚。使用同步体内成像，我们证明了全身性炎症会诱导CCR5依赖性的大脑驻留小胶质细胞迁移到大脑脉管系统。血管相关的小胶质细胞最初通过紧密连接蛋白Claudin-5的表达维持BBB完整性，并与内皮细胞发生物理接触。在持续的炎症过程中，小胶质细胞吞噬了星形胶质细胞的尾脚并损害了血脑屏障功能。我们的研究结果表明，小胶质细胞在维持BBB完整性方面起着双重作用，并具有阐明系统性免疫激活如何影响神经功能的意义。

更新日期：2019-12-20

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