Ellen Orthey

Publications (2)15.63 Total impact

• Article: Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke.

  Mathias Gelderblom, Anna Weymar, Christian Bernreuther, Joachim Velden, Priyadharshini Arunachalam, Karin Steinbach, Ellen Orthey, Thiruma V Arumugam, Frank Leypoldt, Olga Simova, Vivien Thom, Manuel Friese, Immo Prinz, Christoph Hölscher, Markus Glatzel, Thomas Korn, Christian Gerloff, Eva Tolosa, Tim Magnus
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  ABSTRACT: The devastating effect of ischemic stroke is attenuated in mice lacking conventional and unconventional T cells suggesting that inflammation enhances tissue damage in cerebral ischemia. We explored the functional role of αβ and γδ T cells in a murine model of stroke and distinguished two different T cell-dependent proinflammatory pathways in ischemia-reperfusion injury. IFN-γ produced by CD4(+) T cells induced TNF-α production in macrophages, while IL-17A secreted by γδ T cells led to neutrophil recruitment. The synergistic effect of TNF-α and IL-17A on astrocytes resulted in enhanced secretion of CXCL-1, a neutrophil chemoattractant. Application of an IL-17A-blocking antibody within three hours after stroke induction decreased infarct size and improved neurological outcome in the murine model. In autoptic brain tissue of stroke patients, we detected IL-17A positive lymphocytes suggesting that this aspect of the inflammatory cascade is also relevant in the human brain. We propose that selective targeting of IL-17A signaling might provide a new therapeutic option for the treatment of stroke.
  Blood 09/2012; · 9.90 Impact Factor
• Article: Temporal and spatial dynamics of cerebral immune cell accumulation in stroke.

  Mathias Gelderblom, Frank Leypoldt, Karin Steinbach, Doerthe Behrens, Chi-Un Choe, Dominic A Siler, Thiruma V Arumugam, Ellen Orthey, Christian Gerloff, Eva Tolosa, Tim Magnus
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  ABSTRACT: Ischemic stroke leads to significant morbidity and mortality in the Western world. Early reperfusion strategies remain the treatment of choice but can initiate and augment an inflammatory response causing secondary brain damage. The understanding of postischemic inflammation is very limited. The objectives of this study were to define the temporal and spatial infiltration of immune cell populations and their activation patterns in a murine cerebral ischemia-reperfusion injury model. Transient middle cerebral artery occlusion was induced for 1 hour followed by 12-hour to 7-day reperfusion in C57/BL6 mice. Immunohistochemistry and flow cytometry were used to quantify the infiltrating immune cell subsets. Accumulation of microglia and infiltration of the ischemic hemisphere by macrophages, lymphocytes, and dendritic cells (DCs) preceded the neutrophilic influx. DCs were found to increase 20-fold and constituted a substantial proportion of infiltrating cells. DCs exhibited a significant upregulation of major histocompatibility complex II and major histocompatibility complex II high-expressing DCs were found 100 times more abundant than in sham conditions. Upregulation of the costimulatory molecule CD80 was observed in DCs and microglial cells but did not further increase in major histocompatibility complex II high-expressing DCs. No lymphocyte activation was observed. Additionally, regulatory immune cells (natural killer T-cells, CD4(-)/CD8(-)T lymphocytes) cumulated in the ischemic hemisphere. This study provides a detailed analysis of the temporal dynamics of immune cell accumulation in a rodent stroke model. The peculiar activation pattern and massive increase of antigen-presenting cells in temporal conjunction with regulatory cells might provide additional insight into poststroke immune regulation.
  Stroke 04/2009; 40(5):1849-57. · 5.73 Impact Factor