Cargando…

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

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 wi...

Descripción completa

Detalles Bibliográficos
Autores principales: Szalay, Gergely, Martinecz, Bernadett, Lénárt, Nikolett, Környei, Zsuzsanna, Orsolits, Barbara, Judák, Linda, Császár, Eszter, Fekete, Rebeka, West, Brian L., Katona, Gergely, Rózsa, Balázs, Dénes, Ádám
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4857403/
https://www.ncbi.nlm.nih.gov/pubmed/27139776
http://dx.doi.org/10.1038/ncomms11499
_version_ 1782430652446015488
author Szalay, Gergely
Martinecz, Bernadett
Lénárt, Nikolett
Környei, Zsuzsanna
Orsolits, Barbara
Judák, Linda
Császár, Eszter
Fekete, Rebeka
West, Brian L.
Katona, Gergely
Rózsa, Balázs
Dénes, Ádám
author_facet Szalay, Gergely
Martinecz, Bernadett
Lénárt, Nikolett
Környei, Zsuzsanna
Orsolits, Barbara
Judák, Linda
Császár, Eszter
Fekete, Rebeka
West, Brian L.
Katona, Gergely
Rózsa, Balázs
Dénes, Ádám
author_sort Szalay, Gergely
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4857403
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-48574032016-05-23 Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke Szalay, Gergely Martinecz, Bernadett Lénárt, Nikolett Környei, Zsuzsanna Orsolits, Barbara Judák, Linda Császár, Eszter Fekete, Rebeka West, Brian L. Katona, Gergely Rózsa, Balázs Dénes, Ádám Nat Commun Article 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. Nature Publishing Group 2016-05-03 /pmc/articles/PMC4857403/ /pubmed/27139776 http://dx.doi.org/10.1038/ncomms11499 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Szalay, Gergely
Martinecz, Bernadett
Lénárt, Nikolett
Környei, Zsuzsanna
Orsolits, Barbara
Judák, Linda
Császár, Eszter
Fekete, Rebeka
West, Brian L.
Katona, Gergely
Rózsa, Balázs
Dénes, Ádám
Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke
title Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke
title_full Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke
title_fullStr Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke
title_full_unstemmed Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke
title_short Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke
title_sort microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4857403/
https://www.ncbi.nlm.nih.gov/pubmed/27139776
http://dx.doi.org/10.1038/ncomms11499
work_keys_str_mv AT szalaygergely microgliaprotectagainstbraininjuryandtheirselectiveeliminationdysregulatesneuronalnetworkactivityafterstroke
AT martineczbernadett microgliaprotectagainstbraininjuryandtheirselectiveeliminationdysregulatesneuronalnetworkactivityafterstroke
AT lenartnikolett microgliaprotectagainstbraininjuryandtheirselectiveeliminationdysregulatesneuronalnetworkactivityafterstroke
AT kornyeizsuzsanna microgliaprotectagainstbraininjuryandtheirselectiveeliminationdysregulatesneuronalnetworkactivityafterstroke
AT orsolitsbarbara microgliaprotectagainstbraininjuryandtheirselectiveeliminationdysregulatesneuronalnetworkactivityafterstroke
AT judaklinda microgliaprotectagainstbraininjuryandtheirselectiveeliminationdysregulatesneuronalnetworkactivityafterstroke
AT csaszareszter microgliaprotectagainstbraininjuryandtheirselectiveeliminationdysregulatesneuronalnetworkactivityafterstroke
AT feketerebeka microgliaprotectagainstbraininjuryandtheirselectiveeliminationdysregulatesneuronalnetworkactivityafterstroke
AT westbrianl microgliaprotectagainstbraininjuryandtheirselectiveeliminationdysregulatesneuronalnetworkactivityafterstroke
AT katonagergely microgliaprotectagainstbraininjuryandtheirselectiveeliminationdysregulatesneuronalnetworkactivityafterstroke
AT rozsabalazs microgliaprotectagainstbraininjuryandtheirselectiveeliminationdysregulatesneuronalnetworkactivityafterstroke
AT denesadam microgliaprotectagainstbraininjuryandtheirselectiveeliminationdysregulatesneuronalnetworkactivityafterstroke