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

Ventricular hemorrhage causes necrosis of human astrocytes by a cytosolic Ca2+-overload and mitochondrial damage

Meeting Abstract

  • Wolfram Scharbrodt - Department of Neurosurgery, University of Gießen, Germany
  • Yaser Abdallah - Department of Physiology, University of Gießen, Germany
  • Mohammed Miqdad - Department of Physiology, University of Gießen, Germany
  • Sascha A. Kasseckert - Department of Physiology, University of Gießen, Germany
  • Marco Stein - Department of Neurosurgery, University of Gießen, Germany
  • Matthias F. Oertel - Department of Neurosurgery, University of Gießen, Germany

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. DocP1873

DOI: 10.3205/10dgnc344, URN: urn:nbn:de:0183-10dgnc3446

Published: September 16, 2010

© 2010 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

Text

Objective: Ca2+ is a cofactor of many intracellular processes including apoptosis and necrosis. This study’s hypothesis was that bloody CSF from patients after intraventricular hemorrhage (IVH) may cause a Ca2+-rise which induces a mitochondrial dysfunction that results in necrosis in a in-vitro model of human cerebral astrocytes.

Methods: Human astrocytes were incubated with CSF from patients with IVH. In control experiments native CSF was used. Single cell cytosolic Ca2+-concentrations were measured by fura-2 microfluometry. Three blockers were used: Cyclosporin A, APB and suramine that block mitochondrial permeability transition pores (MPTP), endoplasmic reticulum IP3 sensitive Ca2+-channels and ATP-sensitive PY2-rezeptor, respectively. Apopotois and necrosis were evaluated by staining with Hoechst-3342 and propidium iodide, respectively.

Results: Incubation of astrocytes with bloody-CSF provoked an initial Ca2+ peak that was followed by a slow but long lasting Ca2+-rise over the observation period of 60 min. This was also true, when the extracellular Ca2+ was bounded by EDTA. Incubation of the astrocytes with bloody-CSF induced necrosis but not apoptosis. APB and suramin reduced both significantly the Ca2+-rise and the rate of necrosis. Cyclosporin A did not influence the Ca2+-rise but reduced significantly the rate of necrosis.

Conclusions: Bloody CSF induces a Ca2+-overload that leads to necrosis but not apoptosis in human astrocytes via activation of the ATP-sensitive PY2-receptor and Ca2+ release from IP3-dependent intracellular Ca2+-stores. The necrosis is due to Ca2+-dependent opening of MPTP resulting in breakdown of mitochondrial homoeostasis.