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

Author

Listed:
  • Koichiro Haruwaka

    (Kobe University Graduate School of Medicine
    National Institutes of Natural Sciences
    The Graduate School for Advanced Study)

  • Ako Ikegami

    (Kobe University Graduate School of Medicine)

  • Yoshihisa Tachibana

    (Kobe University Graduate School of Medicine)

  • Nobuhiko Ohno

    (Jichi Medical University
    National Institute for Physiological Sciences)

  • Hiroyuki Konishi

    (Nagoya University Graduate School of Medicine)

  • Akari Hashimoto

    (Kobe University Graduate School of Medicine)

  • Mami Matsumoto

    (National Institute for Physiological Sciences
    Nagoya City University Graduate School of Medical Sciences)

  • Daisuke Kato

    (Kobe University Graduate School of Medicine
    Nagoya 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
    The Graduate School for Advanced Study)

  • Hiroaki Wake

    (Kobe University Graduate School of Medicine
    Nagoya University Graduate School of Medicine
    Japan Science and Technology Agency
    Japan Science and Technology Agency)

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.

Suggested Citation

  • Koichiro Haruwaka & Ako Ikegami & Yoshihisa Tachibana & Nobuhiko Ohno & Hiroyuki Konishi & Akari Hashimoto & Mami Matsumoto & Daisuke Kato & Riho Ono & Hiroshi Kiyama & Andrew J. Moorhouse & Junichi N, 2019. "Dual microglia effects on blood brain barrier permeability induced by systemic inflammation," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13812-z
    DOI: 10.1038/s41467-019-13812-z
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    Cited by:

    1. Shannon Tansley & Sonali Uttam & Alba Ureña Guzmán & Moein Yaqubi & Alain Pacis & Marc Parisien & Haley Deamond & Calvin Wong & Oded Rabau & Nicole Brown & Lisbet Haglund & Jean Ouellet & Carlo Santag, 2022. "Single-cell RNA sequencing reveals time- and sex-specific responses of mouse spinal cord microglia to peripheral nerve injury and links ApoE to chronic pain," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Sally H. Mohamed & Man Shun Fu & Sofia Hain & Alanoud Alselami & Eliane Vanhoffelen & Yanjian Li & Ebrima Bojang & Robert Lukande & Elizabeth R. Ballou & Robin C. May & Chen Ding & Greetje Vande Velde, 2023. "Microglia are not protective against cryptococcal meningitis," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Fan Li & Jazlyn Gallego & Natasha N. Tirko & Jenna Greaser & Derek Bashe & Rudra Patel & Eric Shaker & Grace E. Valkenburg & Alanoud S. Alsubhi & Steven Wellman & Vanshika Singh & Camila Garcia Padill, 2024. "Low-intensity pulsed ultrasound stimulation (LIPUS) modulates microglial activation following intracortical microelectrode implantation," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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