title: Intravascular Inflammation Triggers Intracerebral Activated Microglia and Contributes to Secondary Brain Injury After Experimental Subarachnoid Hemorrhage (eSAH).
abstract: Activation of innate immunity contributes to secondary brain injury after experimental subarachnoid hemorrhage (eSAH). Microglia accumulation and activation within the brain has recently been shown to induce neuronal cell death after eSAH. In isolated mouse brain capillaries after eSAH, we show a significantly increased gene expression for intercellular adhesion molecule-1 (ICAM-1) and P-selectin. Hence, we hypothesized that extracerebral intravascular inflammatory processes might initiate the previously reported microglia accumulation within the brain tissue. We therefore induced eSAH in knockout mice for ICAM-1 (ICAM-1-/-) and P-selectin glycoprotein ligand-1 (PSGL-1-/-) to find a significant decrease in neutrophil-endothelial interaction within the first 7 days after the bleeding in a chronic cranial window model. This inhibition of neutrophil recruitment to the endothelium results in significantly ameliorated microglia accumulation and neuronal cell death in knockout animals in comparison to controls. Our results suggest an outside-in activation of the CNS innate immune system at the vessel/brain interface following eSAH. Microglia cells, as part of the brain's innate immune system, are triggered by an inflammatory reaction in the microvasculature after eSAH, thus contributing to neuronal cell death. This finding offers a whole range of new research targets, as well as possible therapy options for patients suffering from eSAH.
authors.affiliation: Experimental Neurosurgery, Charité-Universitätsmedizin Berlin, 10117, Berlin, Germany.|Department of Anaesthesia and Intensive Care Medicine, Universitätsmedizin Göttingen, 37099, Göttingen, Germany.
authors.forename: Etienne
authors.initials: E
authors.lastname: Atangana
authors.affiliation: Experimental Neurosurgery, Charité-Universitätsmedizin Berlin, 10117, Berlin, Germany.|Department of Neurosurgery, Charité-Universitätsmedizin Berlin, 12200, Berlin, Germany.
authors.forename: Ulf C
authors.initials: UC
authors.lastname: Schneider
authors.affiliation: Experimental Neurosurgery, Charité-Universitätsmedizin Berlin, 10117, Berlin, Germany.
authors.forename: Kinga
authors.initials: K
authors.lastname: Blecharz
authors.affiliation: Experimental Neurosurgery, Charité-Universitätsmedizin Berlin, 10117, Berlin, Germany.
authors.forename: Salima
authors.initials: S
authors.lastname: Magrini
authors.affiliation: Experimental Neurosurgery, Charité-Universitätsmedizin Berlin, 10117, Berlin, Germany.
authors.forename: Josephin
authors.initials: J
authors.lastname: Wagner
authors.affiliation: Experimental Neurosurgery, Charité-Universitätsmedizin Berlin, 10117, Berlin, Germany.
authors.forename: Melina
authors.initials: M
authors.lastname: Nieminen-Kelhä
authors.affiliation: Experimental Neurosurgery, Charité-Universitätsmedizin Berlin, 10117, Berlin, Germany.
authors.forename: Irina
authors.initials: I
authors.lastname: Kremenetskaia
authors.affiliation: Department of Neuropathology, Charité-Universitätsmedizin Berlin, 10117, Berlin, Germany.
authors.forename: Frank L
authors.initials: FL
authors.lastname: Heppner
authors.affiliation: Theodor Kocher Institut, Universität Bern, 3012, Bern, Switzerland.
authors.forename: Britta
authors.initials: B
authors.lastname: Engelhardt
authors.affiliation: Experimental Neurosurgery, Charité-Universitätsmedizin Berlin, 10117, Berlin, Germany. peter.vajkoczy@charite.de.|Department of Neurosurgery, Charité-Universitätsmedizin Berlin, 12200, Berlin, Germany. peter.vajkoczy@charite.de.|Department of Neurosurgery, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. peter.vajkoczy@charite.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Vajkoczy
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology*; D016923:Cell Death; D002465:Cell Movement; D004195:Disease Models, Animal; D004660:Encephalitis / Q000378:metabolism / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D006439:Hemodynamics; D007113:Immunity, Innate; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007962:Leukocytes / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000502:physiology*; D055806:Microvessels / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology; D019007:P-Selectin / Q000378:metabolism*; D013345:Subarachnoid Hemorrhage / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1
keywords: Delayed brain injury; Inflammation; Microglia; Subarachnoid hemorrhage