title: Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke.
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.
authors.affiliation: Two-Photon Imaging Center, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony U. 43, Budapest 1083, Hungary.
authors.forename: Gergely
authors.initials: G
authors.lastname: Szalay
authors.affiliation: Laboratory of Neuroimmunology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony U. 43, Budapest 1083, Hungary.
authors.forename: Bernadett
authors.initials: B
authors.lastname: Martinecz
authors.affiliation: Laboratory of Neuroimmunology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony U. 43, Budapest 1083, Hungary.
authors.forename: Nikolett
authors.initials: N
authors.lastname: Lénárt
authors.affiliation: Laboratory of Neuroimmunology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony U. 43, Budapest 1083, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Környei
authors.affiliation: Laboratory of Neuroimmunology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony U. 43, Budapest 1083, Hungary.
authors.forename: Barbara
authors.initials: B
authors.lastname: Orsolits
authors.affiliation: Two-Photon Imaging Center, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony U. 43, Budapest 1083, Hungary.|MTA-PPKE ITK-NAP B - Two-photon measurement Technology Research Group, Pázmány Péter University, Budapest 1083, Hungary.
authors.forename: Linda
authors.initials: L
authors.lastname: Judák
authors.affiliation: Laboratory of Neuroimmunology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony U. 43, Budapest 1083, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Császár
authors.affiliation: Laboratory of Neuroimmunology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony U. 43, Budapest 1083, Hungary.
authors.forename: Rebeka
authors.initials: R
authors.lastname: Fekete
authors.affiliation: Plexxikon, Inc., Berkeley, California 94710, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: West
authors.affiliation: MTA-PPKE ITK-NAP B - Two-photon measurement Technology Research Group, Pázmány Péter University, Budapest 1083, Hungary.
authors.forename: Gergely
authors.initials: G
authors.lastname: Katona
authors.affiliation: Two-Photon Imaging Center, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony U. 43, Budapest 1083, Hungary.|MTA-PPKE ITK-NAP B - Two-photon measurement Technology Research Group, Pázmány Péter University, Budapest 1083, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Rózsa
authors.affiliation: Laboratory of Neuroimmunology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony U. 43, Budapest 1083, Hungary.
authors.forename: Ádám
authors.initials: Á
authors.lastname: Dénes
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D002545:Brain Ischemia / Q000503:physiopathology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism / Q000502:physiology*; D036641:Microscopy, Fluorescence, Multiphoton; D009415:Nerve Net / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology*; D000066829:Neuroprotection / Q000502:physiology; D020521:Stroke / Q000503:physiopathology*; D059008:Time-Lapse Imaging / Q000379:methods
chemical_list: D049452:Green Fluorescent Proteins