gms | German Medical Science

61st Annual Meeting of the German Society of Neurosurgery (DGNC) as part of the Neurowoche 2010
Joint Meeting with the Brazilian Society of Neurosurgery on the 20 September 2010

German Society of Neurosurgery (DGNC)

21 - 25 September 2010, Mannheim

Microglia activation after acute subarachnoid hemorrhage (aSAH) – an intraparenchymal reaction to an extraparenchymal disease

Meeting Abstract

  • Ulf C. Schneider - Neurochirurgische Klinik, Charité – Universitätsmedizin Berlin, Deutschland
  • Anja-Maria Radon - Neurochirurgische Klinik, Charité – Universitätsmedizin Berlin, Deutschland
  • Angelika Gutenberg - Neurochirurgische Klinik, Universitätsmedizin Göttingen, Deutschland
  • Susan Brandenburg - Neurochirurgische Klinik, Charité – Universitätsmedizin Berlin, Deutschland
  • Wolfgang Brück - Abteilung für Neuropathologie, Universitätsmedizin Göttingen, Deutschland
  • Frank Heppner - Institut für Neuropathologie, Charité – Universitätsmedizin Berlin, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010. Mannheim, 21.-25.09.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocV1595

doi: 10.3205/10dgnc070, urn:nbn:de:0183-10dgnc0709

Published: September 16, 2010

© 2010 Schneider et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Objective: Microglia (MG) cells seem to play an important role in the patho-mechanism of a variety of CNS diseases. Here, we hypothesized that an intracerebral activation of the inflammatory cascade may also contribute to brain damage after aSAH. To this end, we evaluated activation of MG, neuronal damage, as well as cytokine expression of MG activation after experimental and human aSAH.

Methods: Three sets of experiments were performed 1.) Experimental aSAH was induced in C57Bl/6 mice using the filament perforation model. After 4, 14 and 28 days brain slices were stained for Iba-1 to detect activated MG and APP to visualize axonal damage. 2.) CD11b-positive MG cells were isolated from murine brains after aSAH on days 4 and 14 using magnetically activated cell sorting (98% purity as assessed by FACS). Quantitative PCR was performed for TNF-alpha, IL-1a, IL-1b, and their corresponding receptors. 3.) Human brain autopsy sections of patients who had died from aSAH (causes other than DIND) were stained for Iba-1 and APP.

Results: In murine brain sections an intraparenchymal accumulation of Iba-1 positive cells was documented which started around day 4 and peaked around day 14 after aSAH (d4/d14/d28: Iba-1 (covered area in sqmm): 0.23±0.04 / 4.13±1.22 / 3.15±2.77) Furthermore, axonal damage as demonstrated by intense APP expression paralleled MG activation (APP (covered area in sqmm): 0.19±0.01 / 3.36±1.01 / 0.27±0.02). In human brain specimens, the relevance of these experimental findings could be confirmed (d4/d14/d28: Iba-1 (cells / hpf): 13.5±8.7 / 73.4±36.8 / 15.7±4.6; APP-activation (arbitrary scale): 0.3/1.8/1.0). Cytokine levels of IL1 a, b and TNF as well as the corresponding receptors (R) in the isolated CD11b positive cells were significantly increased on day 14 after SAH versus sham controls. (IL1a 2.5, IL1b 5.2, TNF 4.1, IL1R2 3.2, TNFR1 2.4, TNFR2 4.1-fold vs. controls)

Conclusions: A significant intraparenchymal accumulation of MG cells was documented after experimental as well as after clinical aSAH. The time course, expression pattern and upregulated transcription of inflammatory cytokines corresponded well with signs of axonal damage. For the first time MG activation as intraparenchymal inflammatory reaction to aSAH was characterized and a hint on the underlying molecular mechanisms could be achieved.