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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

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Effect of deferoxamine on early brain injury following subarachnoid hemorrhage

Meeting Abstract

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  • Jin-Yul Lee - Neurochirurgische Klinik und Poliklinik, Klinikum der Universität Würzburg, Germany; Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA
  • Richard F Keep - Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA
  • Ya Hua - Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA
  • Ralf-Ingo Ernestus - Neurochirurgische Klinik und Poliklinik, Klinikum der Universität Würzburg, Germany
  • Guohua Xi - Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA

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. DocV1596

doi: 10.3205/10dgnc071, urn:nbn:de:0183-10dgnc0715

Published: September 16, 2010

© 2010 Lee 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: The effect of subarachnoid hemoglobin on neuro-glial cells and early brain injury after subarachnoid hemorrhage (SAH) is unclear. The purpose of the current study was to investigate hemoglobin and iron handling after SAH, examine the relationship between iron and neuro-glial cell changes and determine whether an iron chelator, deferoxamine (DFX), can reduce SAH-induced injury.

Methods: SAH was induced in male Sprague-Dawley rats (n=121) using an endovascular perforation technique. Animals were treated with DFX (100 mg/kg) or vehicle. Rats were sacrificed at 6 h, Day 1 and 3 to determine non-heme iron and examine iron-handling proteins using Western-blot and immunohistochemistry. Additionally, 8-hydroxyl-2´-deoxyguanosine (8-OHdG) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining were performed to assess oxidative DNA damage and apoptotic neuronal cell death.

Results: After SAH, marked HO-1 upregulation at Day 3 (P<0.01) was accompanied by elevated non-heme iron (P<0.01). Transferrin (P<0.01), transferrin receptor (P<0.05) and ferritin levels (P<0.01) were all increased on Day 3 following SAH. DFX treatment reduced SAH-induced mortality (12% vs. 29%), brain non-heme iron concentration, iron-handling protein expression and oxidative stress and neuronal cell death at Day 3 (P<0.01) following SAH.

Conclusions: These results suggest that iron overload in the acute phase of SAH causes oxidative injury leading to neuronal cell death. Deferoxamine effectively reduced oxidative stress and neuronal cell death, and may be a potential therapeutic agent for SAH.