gms | German Medical Science

58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

26. bis 29.04.2007, Leipzig

Role of the Apoptosis Inducing Factor (AIF) for neuronal cell death following traumatic brain injury

Rolle von Apoptose induzierendem Faktor (AIF) für den neuronalen Zelltod nach Schädel-Hirn-Trauma

Meeting Abstract

  • corresponding author A. Ardeshiri - Neurochirurgische Klinik, Klinikum der Universität München - Großhadern
  • A. Ardeshiri - Neurochirurgische Klinik, Klinikum der Universität München - Großhadern
  • E. J. Slemmer - Erasmus MC, University of Rotterdam, Niederlande
  • C. Culmsee - Institut für Pharmazeutische Biologie, LMU München
  • J. T. Weber - Erasmus MC, University of Rotterdam, Niederlande
  • N. Plesnila - Neurochirurgische Klinik, Klinikum der Universität München - Großhadern

Deutsche Gesellschaft für Neurochirurgie. 58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC). Leipzig, 26.-29.04.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. DocFR.06.09

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2007/07dgnc104.shtml

Veröffentlicht: 11. April 2007

© 2007 Ardeshiri 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 vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: Apoptosis inducing factor (AIF), a caspase-independent cell death protein, translocates from mitochondria to the nucleus in injured cells after traumatic brain injury. Results from in vivo studies suggest that this phenomenon occurs in neurons. In order to further investigate the role of AIF in neurons and astrocytes we investigated the influence of AIF expression on cell death in an in vitro trauma model.

Methods: Primary cultured mouse neurons and glial cells were subjected to trauma by membrane stretch injury. Mild (5.5 mm membrane stretch) or moderate (6.5 mm) trauma was applied. Cells were treated with AIF-siRNA and mutant-siRNA (control) in order to downregulate physiological AIF protein levels as demonstrated by PCR and Western blot analysis. Neurons and astrocytes were identified by MAP-2 and GFAP immunofluorescence, respectively. AIF translocation from mitochondria to the nucleus was shown by immunocytochemistry for AIF and DAPI nuclear staining.

Results: Immunofluorescence showed that translocation of AIF occurred only in neurons and not in glial cells. Both, AIF mRNA and AIF protein were downregulated by AIF-siRNA (-80%). The number of cells showing membrane damage was significantly decreased by AIF-siRNA (-26% for mild and -56% for moderate trauma) and the number of surviving neurons was significantly increased (p<0.001).

Conclusions: The present study proves that translocation of AIF 1) occurs only in neurons and not in astrocytes and 2) leads to neuronal cell death after traumatic cell injury. Therefore inhibition of AIF by AIF-siRNA or other means may be a therapeutic option for the treatment of secondary neuronal cell death following traumatic brain injury.