Intravascular Inflammation Triggers Intracerebral Activated Microglia and Contributes to Secondary Brain Injury After Ex
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ORIGINAL ARTICLE
Intravascular Inflammation Triggers Intracerebral Activated Microglia and Contributes to Secondary Brain Injury After Experimental Subarachnoid Hemorrhage (eSAH) Etienne Atangana 1,2 & Ulf C. Schneider 1,3 & Kinga Blecharz 1 & Salima Magrini 1 & Josephin Wagner 1 & Melina Nieminen-Kelhä 1 & Irina Kremenetskaia 1 & Frank L. Heppner 4 & Britta Engelhardt 5 & Peter Vajkoczy 1,3,6
Received: 11 July 2016 / Revised: 11 July 2016 / Accepted: 14 July 2016 # Springer Science+Business Media New York 2016
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 Etienne Atangana and Ulf C. Schneider contributed equally to this work. Electronic supplementary material The online version of this article (doi:10.1007/s12975-016-0485-3) contains supplementary material, which is available to authorized users. * Peter Vajkoczy [email protected] 1
Experimental Neurosurgery, Charité–Universitätsmedizin Berlin, 10117 Berlin, Germany
2
Department of Anaesthesia and Intensive Care Medicine, Universitätsmedizin Göttingen, 37099 Göttingen, Germany
3
Department of Neurosurgery, Charité–Universitätsmedizin Berlin, 12200 Berlin, Germany
4
Department of Neuropathology, Charité–Universitätsmedizin Berlin, 10117 Berlin, Germany
5
Theodor Kocher Institut, Universität Bern, 3012 Bern, Switzerland
6
Department of Neurosurgery, Charité–Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
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. Keywords Microglia . Inflammation . Subarachnoid hemorrhage . Delayed brain injury
Introduction Secondary brain injury is the most relevant contributor to poor clinical outcome after aneurysmal subarachnoid hemorrhage (SAH),
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