gms | German Medical Science

59th Annual Meeting of the German Society of Neurosurgery (DGNC)
3rd Joint Meeting with the Italian Neurosurgical Society (SINch)

German Society of Neurosurgery (DGNC)

1 - 4 June 2008, Würzburg

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Gene expression analysis shows the involvement of antigen presenting cells in intracranial aneurysm formation

Genexpressionsanalysen weisen auf die Beteiligung von Antigen-präsentierende Zellen bei der Formation intrakranieller Aneurysmen hin

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  • corresponding author B. Krischek - Klinik für Neurochirurgie, Universitätsklinikum Tübingen
  • H. Kasuya - Department of Neurosurgery, Tokyo Women's Medical University, Japan
  • I. Inoue - Division of Molecular Life Science, Tokai University, Japan
  • M. Tatagiba - Klinik für Neurochirurgie, Universitätsklinikum Tübingen

Deutsche Gesellschaft für Neurochirurgie. Società Italiana di Neurochirurgia. 59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch). Würzburg, 01.-04.06.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. DocSO.04.10

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2008/08dgnc033.shtml

Published: May 30, 2008

© 2008 Krischek et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objective: To study the molecular processes involved in intracranial aneurysm formation, a gene expression analysis of a set of three different tissue samples was performed.

Methods: Using a dye swap technique, tissue samples of six ruptured and four unruptured aneurysms, as well as four intracerebral arteries serving as controls, were profiled using oligonucleotide microarrays. Differentially expressed genes were extracted comparing the expression ratio between the aneurysm and control tissue. Subsequently they were grouped according to the gene ontology classification. Focussing on the differentially expressed genes, a computational pathway analysis tool identified specific regulatory networks and pathways that may play a role in intracranial aneurysm formation. As a control we performed RT-PCR and immunohistochemical studies.

Results: Analysis of aneurysmal and control tissue revealed 521 differentially expressed genes. The most significantly associated gene ontology term was antigen processing (P=1.64E-16). Further network-based analysis showed the top scoring regulatory functional network to be built around overexpressed major histocompatibility class (MHC) I and II complex related genes. The canonical pathway “Antigen Presentation”was to confirmed have the highest upregulation in IA tissue (P=7.3E-10). Real time RT-PCR showed significant overexpression of MHC class II genes. Immunohistochemical staining showed strong positivity for MHC II molecule specific antibody (HLA II), for CD68 (macrophages, monocytes), for CD45RO (T-cells) and HLA I antibody.

Conclusions: Our results offer strong evidence for MHC class II gene overexpression in intracranial aneurysm tissue and for the fact that antigen presenting cells (macrophages, monocytes) play a key role in intracranial aneurysm formation.