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Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke

Author

Listed:
  • Gergely Szalay

    (Two-Photon Imaging Center, Institute of Experimental Medicine, Hungarian Academy of Sciences)

  • Bernadett Martinecz

    (Laboratory of Neuroimmunology, Institute of Experimental Medicine, Hungarian Academy of Sciences)

  • Nikolett Lénárt

    (Laboratory of Neuroimmunology, Institute of Experimental Medicine, Hungarian Academy of Sciences)

  • Zsuzsanna Környei

    (Laboratory of Neuroimmunology, Institute of Experimental Medicine, Hungarian Academy of Sciences)

  • Barbara Orsolits

    (Laboratory of Neuroimmunology, Institute of Experimental Medicine, Hungarian Academy of Sciences)

  • Linda Judák

    (Two-Photon Imaging Center, Institute of Experimental Medicine, Hungarian Academy of Sciences
    MTA-PPKE ITK-NAP B - Two-photon measurement Technology Research Group, Pázmány Péter University)

  • Eszter Császár

    (Laboratory of Neuroimmunology, Institute of Experimental Medicine, Hungarian Academy of Sciences)

  • Rebeka Fekete

    (Laboratory of Neuroimmunology, Institute of Experimental Medicine, Hungarian Academy of Sciences)

  • Brian L. West

    (Plexxikon, Inc.)

  • Gergely Katona

    (MTA-PPKE ITK-NAP B - Two-photon measurement Technology Research Group, Pázmány Péter University)

  • Balázs Rózsa

    (Two-Photon Imaging Center, Institute of Experimental Medicine, Hungarian Academy of Sciences
    MTA-PPKE ITK-NAP B - Two-photon measurement Technology Research Group, Pázmány Péter University)

  • Ádám Dénes

    (Laboratory of Neuroimmunology, Institute of Experimental Medicine, Hungarian Academy of Sciences)

Abstract

Microglia are the main immune cells of the brain and contribute to common brain diseases. However, it is unclear how microglia influence neuronal activity and survival in the injured brain in vivo. Here we develop a precisely controlled model of brain injury induced by cerebral ischaemia combined with fast in vivo two-photon calcium imaging and selective microglial manipulation. We show that selective elimination of microglia leads to a striking, 60% increase in infarct size, which is reversed by microglial repopulation. Microglia-mediated protection includes reduction of excitotoxic injury, since an absence of microglia leads to dysregulated neuronal calcium responses, calcium overload and increased neuronal death. Furthermore, the incidence of spreading depolarization (SD) is markedly reduced in the absence of microglia. Thus, microglia are involved in changes in neuronal network activity and SD after brain injury in vivo that could have important implications for common brain diseases.

Suggested Citation

  • Gergely Szalay & Bernadett Martinecz & Nikolett Lénárt & Zsuzsanna Környei & Barbara Orsolits & Linda Judák & Eszter Császár & Rebeka Fekete & Brian L. West & Gergely Katona & Balázs Rózsa & Ádám Déne, 2016. "Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke," Nature Communications, Nature, vol. 7(1), pages 1-13, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11499
    DOI: 10.1038/ncomms11499
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    Cited by:

    1. Xiaotao Zhang & Huaming Li & Yichen Gu & An Ping & Jiarui Chen & Qia Zhang & Zhouhan Xu & Junjie Wang & Shenjie Tang & Rui Wang & Jianan Lu & Lingxiao Lu & Chenghao Jin & Ziyang Jin & Jianmin Zhang & , 2025. "Repair-associated macrophages increase after early-phase microglia attenuation to promote ischemic stroke recovery," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    2. Pasqualina Colella & Ruhi Sayana & Maria Valentina Suarez-Nieto & Jolanda Sarno & Kwamina Nyame & Jian Xiong & Luisa Natalia Pimentel Vera & Jessica Arozqueta Basurto & Marco Corbo & Anay Limaye & Kar, 2024. "CNS-wide repopulation by hematopoietic-derived microglia-like cells corrects progranulin deficiency in mice," Nature Communications, Nature, vol. 15(1), pages 1-26, December.
    3. Zhongxiao Fu & Mallikarjunarao Ganesana & Philip Hwang & Xiao Tan & Melissa Marie Kinkaid & Yu-Yo Sun & Emily Bian & Aden Weybright & Hong-Ru Chen & Katia Sol-Church & Ukpong B. Eyo & Clare Pridans & , 2025. "Microglia modulate the cerebrovascular reactivity through ectonucleotidase CD39," Nature Communications, Nature, vol. 16(1), pages 1-15, December.

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