gms | German Medical Science

56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
3èmes journées françaises de Neurochirurgie (SFNC)

Deutsche Gesellschaft für Neurochirurgie e. V.
Société Française de Neurochirurgie

07. bis 11.05.2005, Strasbourg

Role of apoptosis inducing factor (AIF) after traumatic brain injury (TBI) in mice

Einfluss von Apoptose induzierendem Faktor (AIF) nach Schädel-Hirn-Trauma bei Mäusen

Meeting Abstract

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  • corresponding author A. Ardeshiri - Institute for Surgical Research, University of Munich
  • C. Zhu - Perinatal Center, Department of Physiology, Göteborg University, Sweden
  • K. Blomgren - Perinatal Center, Department of Physiology, Göteborg University, Sweden
  • N. Plesnila - Institute for Surgical Research, University of Munich

Deutsche Gesellschaft für Neurochirurgie. Société Française de Neurochirurgie. 56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3èmes journées françaises de Neurochirurgie (SFNC). Strasbourg, 07.-11.05.2005. Düsseldorf, Köln: German Medical Science; 2005. DocP051

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2005/05dgnc0319.shtml

Veröffentlicht: 4. Mai 2005

© 2005 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

Traumatic brain injury (TBI) leads to secondary brain damage. Apoptosis like mechanisms are involved in this process. Two main pathways, caspase-dependent and caspase-independent, are responsible for secondary brain damage. We have therefore investigated the influence of the caspase-independent factor AIF on secondary brain damage after TBI.

Methods

In one part of the study C57/Bl6 mice (n=30) were craniotomized and subjected to controlled cortical impact (CCI; 8m/s, 1mm). Sham operated animals (n=6) were only craniotomized. The craniotomy was closed and brains were removed 15 min, 2, 6, 12 and 24 h after trauma. Before removing of the brains animals were perfusion-fixed with 4% paraformaldehyde. Brain sections were stained for AIF and different nuclear and mitochondrial markers. In the second part of the study wild type (wt) littermates and AIF-deficient mice (each n=5) were subjected to CCI. Contusion volumes were assessed 24 h after trauma and compared to a group of animals (n=5, brain removed 15 min after CCI) with primary brain damage only.

Results

Immunohistochemistry showed translocation of AIF from mitochondria to the nucleus after TBI. The number of cells showing positive staining for AIF in the nucleus increased with time. In wt mice the contusion increased to 161.3% (33.7±1.9 mm3) 24 h after trauma while in AIF deficient mice contusion just increased to 125.9% (26.3±2.6 mm3, -58% vs. control, p<0.01) compared to its initial volume 15 min after CCI (20.9±2.4 mm3).

Conclusions

These findings demonstrate that the caspase-independent factor AIF is released from mitochondria and translocates to the nucleus and that this translocation is associated with apoptosis-like neuronal cell death after TBI. Therefore AIF might represent a target molecule for the development of drugs against secondary brain damage after TBI.