Artikel
Effect of deferoxamine on early brain injury following subarachnoid hemorrhage
Suche in Medline nach
Autoren
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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
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Richard F Keep
- Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA
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Ya Hua
- Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA
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Ralf-Ingo Ernestus
- Neurochirurgische Klinik und Poliklinik, Klinikum der Universität Würzburg, Germany
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Guohua Xi
- Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA
| Veröffentlicht: | 16. September 2010 |
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Gliederung
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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.
