Hemoglobin and iron handling in brain after subarachnoid hemorrhage and the effect of deferoxamine on early brain injury.
Hemoglobin and iron handling in brain after subarachnoid hemorrhage and the effect of deferoxamine on early brain injury.
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DOI：
10.1038/jcbfm.2010.137
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发表时间：
2010-11
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影响因子：
--
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中科院分区：
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本研究的目的是研究蛛网膜下腔出血（SAH）后血红蛋白和铁处理，检查铁和神经胶质细胞变化之间的关系，并确定去铁胺（DFX）是否可以减少SAH诱导的损伤。使用血管内穿孔技术在Sprague-Dawley大鼠（n=110）中诱导SAH。在SAH诱导后2小时和6小时用DFX（100 mg/kg）或媒介物处理动物，随后每12小时处理一次，持续3天。在6小时，第1和3天处死大鼠，以确定非血红素铁和检查铁处理蛋白，使用蛋白质印迹和免疫组化。8-羟基-2 ′-脱氧鸟苷和TUNEL染色检测氧化性DNA损伤和神经细胞凋亡。SAH后第3天HO-1表达显著上调（P<0.01），同时伴有非血红素铁（P<0.01）、转铁蛋白（P<0.01）、转铁蛋白受体（P<0.05）和铁蛋白（P<0.01）水平升高。DFX治疗降低了SAH诱导的死亡率（12% vs.29%，P<0.05），脑非血红素铁浓度，铁处理蛋白表达，氧化应激和SAH后第3天的神经元细胞死亡（P<0.01）。这些结果表明，SAH急性期的铁过载引起氧化损伤，导致神经元细胞死亡。去铁胺能有效地降低氧化应激和神经细胞死亡，可能是一种潜在的治疗SAH的药物。
The purpose of this study was to investigate hemoglobin and iron handling after subarachnoid hemorrhage (SAH), examine the relationship between iron and neuro-glial cell changes and determine whether deferoxamine (DFX) can reduce SAH-induced injury. 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 h and 6 h after SAH induction followed by every 12 h for 3 days. 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. 8-Hydroxyl-2′-deoxyguanosine and TUNEL staining were performed to assess oxidative DNA damage and apoptotic neuronal cell death. 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). DFX treatment reduced SAH-induced mortality (12% vs. 29%, P<0.05), brain non-heme iron concentration, iron-handling protein expression, oxidative stress and neuronal cell death at Day 3 (P<0.01) following 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.
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影响因子：
--
作者：
Nina, P;Schisano, G;Demurtas, F
通讯作者：
Demurtas, F
影响因子：
8.3
作者：
PALMER, C;ROBERTS, RL;BERO, C
通讯作者：
BERO, C
影响因子：
4.1
作者：
Nakamura, T;Keep, RF;Xi, GH
通讯作者：
Xi, GH
影响因子：
6.3
作者：
Endo, Hidenori;Nito, Chikako;Chan, Pak H.
通讯作者：
Chan, Pak H.
DOI：
10.1073/pnas.88.3.688
发表时间：
1991-02-01
影响因子：
11.1
作者：
EISENSTEIN, RS;GARCIAMAYOL, D;MUNRO, HN
通讯作者：
MUNRO, HN