title: Microglia inflict delayed brain injury after subarachnoid hemorrhage.
abstract: Inflammatory changes have been postulated to contribute to secondary brain injury after aneurysmal subarachnoid hemorrhage (SAH). In human specimens after SAH as well as in experimental SAH using mice, we show an intracerebral accumulation of inflammatory cells between days 4 and 28 after the bleeding. Using bone marrow chimeric mice allowing tracing of all peripherally derived immune cells, we confirm a truly CNS-intrinsic, microglial origin of these immune cells, exhibiting an inflammatory state, and rule out invasion of myeloid cells from the periphery into the brain. Furthermore, we detect secondary neuro-axonal injury throughout the time course of SAH. Since neuronal cell death and microglia accumulation follow a similar time course, we addressed whether the occurrence of activated microglia and neuro-axonal injury upon SAH are causally linked by depleting microglia in vivo. Given that the amount of neuronal cell death was significantly reduced after microglia depletion, we conclude that microglia accumulation inflicts secondary brain injury after SAH.
authors.affiliation: Department of Neurosurgery, Charité, Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Ulf C
authors.initials: UC
authors.lastname: Schneider
authors.forename: Anja-Maria
authors.initials: AM
authors.lastname: Davids
authors.forename: Susan
authors.initials: S
authors.lastname: Brandenburg
authors.forename: Annett
authors.initials: A
authors.lastname: Müller
authors.forename: Anna
authors.initials: A
authors.lastname: Elke
authors.forename: Salima
authors.initials: S
authors.lastname: Magrini
authors.forename: Etienne
authors.initials: E
authors.lastname: Atangana
authors.forename: Kati
authors.initials: K
authors.lastname: Turkowski
authors.forename: Tobias
authors.initials: T
authors.lastname: Finger
authors.forename: Angelika
authors.initials: A
authors.lastname: Gutenberg
authors.forename: Claire
authors.initials: C
authors.lastname: Gehlhaar
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
authors.forename: Frank L
authors.initials: FL
authors.lastname: Heppner
authors.forename: Peter
authors.initials: P
authors.lastname: Vajkoczy
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000473:pathology / Q000502:physiology*; D008875:Middle Aged; D015213:Neuroimmunomodulation / Q000502:physiology; D009474:Neurons / Q000473:pathology / Q000502:physiology; D013345:Subarachnoid Hemorrhage / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D018183:Transplantation Chimera
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D016207:Cytokines; D008840:Microfilament Proteins; D049452:Green Fluorescent Proteins