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62nd Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Polish Society of Neurosurgeons (PNCH)

German Society of Neurosurgery (DGNC)

7 - 11 May 2011, Hamburg

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Ventricular hemorrhage results in opening of IP3-dependent- and L-type- Ca2+-channels leading to a breakdown of the mitochondrial membrane potential and necrosis of human astrocytes

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  • W. Scharbrodt - Neurochirurgische Klinik, Universitätsklinikum Gießen und Marburg, Gießen
  • S.A. Kasseckert - Abteilung für Physiologie, Universitätsklinikum Gießen und Marburg, Gießen
  • Y. Abdallah - Abteilung für Physiologie, Universitätsklinikum Gießen und Marburg, Gießen
  • T. Shahzad - Neurochirurgische Klinik, Universitätsklinikum Gießen und Marburg, Gießen
  • M. Stein - Neurochirurgische Klinik, Universitätsklinikum Gießen und Marburg, Gießen
  • M.F. Oertel - Neurochirurgische Klinik, Universitätsklinikum Gießen und Marburg, Gießen

Deutsche Gesellschaft für Neurochirurgie. Polnische Gesellschaft für Neurochirurgen. 62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH). Hamburg, 07.-11.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. DocDI.05.03

doi: 10.3205/11dgnc128, urn:nbn:de:0183-11dgnc1280

Published: April 28, 2011

© 2011 Scharbrodt 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: Ca2+-is a cofactor of many cellular processes including apoptosis and necrosis. This study’s hypothesis was that bloody CSF from patients after intraventricular hemorrhage causes a cytosolic Ca2+-overload due to opening of IP3 sensitive- or L-Type- Ca2+ -channels. This Ca2+-rise may induce a breakdown of the mitochondrial membrane potential leading to an energy crisis and necrosis of the cells in a in-vitro model of human cerebral astrocytes.

Methods: Human astrocytes were incubated with CSF from patients with intraventricular hemorrhage. In control experiments, native CSF was used. Single cell cytosolic Ca2+-concentrations were measured by fura-2 microfluometry, the membrane potential of the mitochondria by JC-1. Two blockers were used: nimodipine and xestospongin D that block the L-Type Ca2+-channels and the endoplasmic reticulum IP3 sensitive Ca2+-channels, respectively. Apopotosis and necrosis were evaluated by staining with Hoechst-3342 and propidium iodide.

Results: Incubation of astrocytes with bloody-CSF led to an initial Ca2+ peak and then provoked a slow but long lasting Ca2+-rise over the observation period of 60 min and a breakdown of the mitochondrial membrane potential. Necrosis, but not apoptosis of the cells, was recorded. In contrast, native CSF induced neither a significant Ca2+ rise nor apoptosis or necrosis of the astrocytes. Nimodipine or xestospongin D blocked the Ca2+-rise and reduced necrosis significantly.

Conclusions: Bloody CSF induces opening of L-Type Ca2+-channels and IP3-dependent Ca2+-channels. This leads to a cytosolic Ca2+-overload of human astrocytes and a breakdown of the mitochondrial membrane potential. The subsequent energy crisis results in necrosis of the cells.