期刊
NEUROSCIENCE LETTERS
卷 379, 期 2, 页码 96-100出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2004.12.080
关键词
hypoxia-ischemia; brain injury; neonate; hypoxia-inducible factor-1 alpha; desferoxamine; neuroprotection
资金
- NICHD NIH HHS [HD-07162] Funding Source: Medline
- NINDS NIH HHS [NS35902, NS33997] Funding Source: Medline
The newborn brain has increased vulnerability to hypoxia-ischemia from maturational differences in the oxidative stress response. We hypothesized that desferoxamine (DFO), an iron chelator, would provide protection in an in vitro model of ischemia in part through activation of the hypoxia-inducible gene hypoxia-inducible factor-1 alpha (HIF- 1 alpha). Hippocampal neurons from E 16 CD1 mice were exposed to 3 h of oxygen and glucose deprivation with and without pretreatment with 10 mmol/L DFO in the presence and absence of 2 mu mol/L antisense oligonucleotides specific for HIF-1 alpha (antiHIF-1 alpha). DFO pretreatment resulted in 45 % reduction in cell death (p = 0.006). This protection was diminished with transfection of antiHIF- 1 alpha (p = 0.049). Blocking HIF- 1 alpha reduces DFO protection suggesting that DFO protects through iron chelation and HIF- 1 alpha induction. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
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