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

被引：648

作者：

Haruwaka, Koichiro ^{[1
,2
,3
]}

Ikegami, Ako ^{[1
]}

Tachibana, Yoshihisa ^{[1
]}

Ohno, Nobuhiko ^{[4
,5
]}

Konishi, Hiroyuki ^{[6
]}

Hashimoto, Akari ^{[1
]}

Matsumoto, Mami ^{[7
,8
]}

Kato, Daisuke ^{[1
,9
]}

Ono, Riho ^{[1
]}

Kiyama, Hiroshi ^{[6
]}

Moorhouse, Andrew J. ^{[10
]}

Nabekura, Junichi ^{[2
,3
]}

Wake, Hiroaki ^{[1
,9
,11
,12
]}

机构：

[1] Kobe Univ, Div Syst Neurosci, Grad Sch Med, Kobe, Hyogo, Japan

[2] Natl Inst Nat Sci, Natl Inst Physiol Sci, Div Homeostat Dev, Okazaki, Aichi, Japan

[3] Grad Sch Adv Study, Dept Physiol Sci, Hayama, Kanagawa, Japan

[4] Jichi Med Univ, Dept Anat, Div Histol & Cell Biol, Shimotsuke, Tochigi, Japan

[5] Natl Inst Physiol Sci, Div Ultrastruct Res, Okazaki, Aichi, Japan

[6] Nagoya Univ, Dept Funct Anat & Neurosci, Grad Sch Med, Nagoya, Aichi, Japan

[7] Natl Inst Physiol Sci, Support Ctr Brain Res, Sect Electron Microscopy, Okazaki, Aichi, Japan

[8] Nagoya City Univ, Dept Dev & Regenerat Biol, Grad Sch Med Sci, Nagoya, Aichi, Japan

[9] Nagoya City Univ, Dept Anat & Mol Cell Biol, Grad Sch Med, Nagoya, Aichi, Japan

[10] Univ New South Wales, Sch Med Sci, Sydney, NSW, Australia

[11] Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol, Saitama, Japan

[12] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol, Saitama, Japan

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

关键词：

IN-VIVO; MINOCYCLINE; CELLS; DISEASE; LOCALIZATION; ACTIVATION; MORPHOLOGY; PERICYTES; DYNAMICS; NEURONS;

D O I：

10.1038/s41467-019-13812-z

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：17

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