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

Gergely Szalay, Bernadett Martinecz, Nikolett Lénárt, Zsuzsanna Környei, Barbara Orsolits, Linda Judák, Eszter Császár, Rebeka Fekete, Brian L. West, Gergely Katona, B. Rózsa, Ádám Dénes

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145 Citations (Scopus)

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.

Original languageEnglish
Article number11499
JournalNature Communications
Volume7
DOIs
Publication statusPublished - May 3 2016

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Szalay, G., Martinecz, B., Lénárt, N., Környei, Z., Orsolits, B., Judák, L., Császár, E., Fekete, R., West, B. L., Katona, G., Rózsa, B., & Dénes, Á. (2016). Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke. Nature Communications, 7, [11499]. https://doi.org/10.1038/ncomms11499