gms | German Medical Science

57. Jahrestagung der Deutschen Gesellschaft für Neuropathologie und Neuroanatomie (DGNN)

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie

12. - 15.09.2012, Erlangen

Banner: 57. Jahrestagung der Deutschen Gesellschaft für Neuropathologie und Neuroanatomie

Challenging the dogma of neutrophil invasion in ischemic stroke

Meeting Abstract

  • presenting/speaker Rudi Beschorner - Institute of Pathology and Neuropathology, Tübingen, Germany
  • Patrick N. Harter - Goethe University Frankfurt, Edinger Institute (Neurological Institute), Frankfurt, Germany
  • Gaby Enzmann - Theodor Kocher Institute, University of Bern, Bern, Switzerland
  • Caroline Mysiorek - Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Münster, Germany
  • Roser G. Mendiz - Theodor Kocher Institute, University of Bern, Bern, Switzerland
  • Yu-Jung Cheng - Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Münster, Germany
  • Sharang Ghavampour - Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Münster, Germany
  • Melanie-Jane Hannocks - Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Münster, Germany
  • Vincent Prinz - Department of Neurology, Charité University, Berlin, Germany
  • Ulrich Dirnagl - Department of Neurology, Charité University, Berlin, Germany
  • Matthias Endres - Department of Neurology, Charité University, Berlin, Germany; Center for Stroke Research Berlin, Charité University, Berlin, Germany
  • Marco Prinz - Department of Neuropathology, University of Freiburg, Freiburg, Germany
  • Britta Engelhardt - Theodor Kocher Institute, University of Bern, Bern, Switzerland
  • Lydia Sorokin - Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Münster, Germany
  • Michel Mittelbronn - Goethe University Frankfurt, Edinger Institute (Neurological Institute), Frankfurt, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Erlangen, 12.-15.09.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12dgnnPP7.3

DOI: 10.3205/12dgnn129, URN: urn:nbn:de:0183-12dgnn1295

Veröffentlicht: 11. September 2012

© 2012 Beschorner et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

It is a well accepted dogma that neutrophils invade the CNS parenchyma in early stroke events starting approximately 15 h and ceasing around the 5th day after stroke onset thereby contributing to blood-barrier breakdown and reperfusion injury. In the present study, we aimed to reevaluate the temporo-spatial distribution of neutrophils in 25 well-characterized, early human stroke cases (17 stage I and 8 combined stage I/II cases) by means of histology, immunohistochemical and immunofluorescent stainings since currently more precise methods are available to define cellular subtypes and localisation. In our cohort, a slight accumulation of CD15-positive neutrophils was observed within blood vessels and the perivascular space. However, virtually no granulocytic infiltration of the CNS parenchyma independent from the localization (ischemic center, penumbra or remote normal appearing tissue) was seen. The major part of CD15-positive granulocytes passing the endothelium was still localized inside the parenchymal, collagen IV-positive basement membrane. Interestingly, at all time points the amount of neutrophils in the CNS parenchyma did not exceed CD68-positive MØs or CD3-positive T-cells. A small cellular fraction within the CNS parenchyma histologically appearing as neutrophils could be characterized as cleaved caspase 3-positive cells indicating apoptosis. Our findings in human stroke cases could be corroborated in a murine transient middle cerebral artery occlusion (tMCAO) model with the use of markers for cellular and basement membrane constituents. In the tMCAO model high-resolution confocal microscopy revealed that neutrophils rarely, if ever, gain access to the CNS parenchyma after the ischemic insult. Furthermore, in vitro studies showed that hypoxia alone failed to induce neutrophil migration across the endothelial monolayer under reestablished flow conditions. In conclusion, our findings shed a new light on the potential role of neutrophils in early stroke events and might at least partly explain several disappointing results in clinical trials that tried to target neutrophils to reduce infarct volume.