Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 30, Issue 11, Pages 1793-1803Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/jcbfm.2010.137
Keywords
deferoxamine; hemoglobin; iron; oxidative injury; subarachnoid hemorrhage
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Funding
- Else Kroner-Fresenius-Stiftung, Bad Homburg, Germany
- Stiftung Neurochirurgische Forschung of German Society of Neurosurgery
- National Institutes of Health (NIH) [NS-017760, NS-039866, NS-052510, NS-057539]
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The purpose of this study was to investigate hemoglobin and iron handling after subarachnoid hemorrhage (SAH), examine the relationship between iron and neuroglial cell changes, and determine whether deferoxamine (DFX) can reduce SAH-induced injury. The SAH was induced in Sprague-Dawley rats (n = 110) using an endovascular perforation technique. Animals were treated with DFX (100 mg/kg) or vehicle 2 and 6 hours after SAH induction followed by every 12 hours for 3 days. Rats were killed at 6 hours, Days 1 and 3 to determine nonheme iron and examine iron-handling proteins using Western blot and immunohistochemistry. 8-Hydroxyl-2'-deoxyguanosine and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining were performed to assess oxidative DNA damage and neuronal cell death. After SAH, marked heme-oxygenase-1 (HO-1) upregulation at Day 3 (P < 0.01) was accompanied by elevated nonheme iron (P < 0.01), transferrin (Tf) (P < 0.01), Tf receptor (P < 0.05), and ferritin levels (P < 0.01). Deferoxamine treatment reduced SAH-induced mortality (12% versus 29%, P < 0.05), brain nonheme iron concentration, iron-handling protein expression, oxidative stress, and neuronal cell death at Day 3 (P < 0.01) after SAH. 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. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 1793-1803; doi:10.1038/jcbfm.2010.137; published online 25 August 2010
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