Role of iron in brain injury after intraventricular hemorrhage.

Role of iron in brain injury after intraventricular hemorrhage.
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DOI:
10.1161/strokeaha.110.602755
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发表时间:
2011-02
期刊:
影响因子:
8.3
通讯作者:
Xi G
Xi G
中科院分区:
医学1区
文献类型:
--
作者:
Chen Z;Gao C;Hua Y;Keep RF;Muraszko K;Xi G

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脑出血(ICH)后脑室内出血范围扩大是预后不良的预测因素,铁负荷过多导致脑出血后的脑损伤。本研究在一个脑室出血(IVH)的大鼠模型中研究了铁在脑室扩张和神经元死亡中的作用。本研究分为两个部分。首先,雄性SD大鼠将200μ的L自体血液或生理盐水注入右侧脑室,并在不同的时间点进行安乐死。对大鼠进行磁共振成像,并使用大脑进行蛋白质印迹分析、免疫组织化学、组织学和脑组织非血红素铁的测量。其次,大鼠进行IVH,给予去铁胺(DFX)或赋形剂治疗,4周后处死大鼠,测量脑组织和侧脑室大小。IVH可导致脑铁积聚,双侧侧脑室扩大,海马区脑组织丢失。铁的积累与血红素加氧酶-1和铁蛋白的上调有关。全身DFX治疗减少了IVH所致的脑室扩大(28天:32.7±10.6 mm3vs.43.8±9.7 mm3,n=8-9,p<0.05)和海马脑组织丢失(海马区体积:89.0±2.7 mm3vs.85.2±4.1 mm3,p<0.05)。铁在IVH后的脑损伤中起到了作用。DFX可能是治疗脑出血后IVH或脑室内扩张的一种方法。
Intraventricular extension of hemorrhage is a predictor of poor outcome in intracerebral hemorrhage (ICH) and iron overload contributes to brain injury after ICH. The current study investigated the role of iron in ventricular dilatation and neuronal death in a rat model of intraventricular hemorrhage (IVH). There were two parts in this study. First, male Sprague-Dawley rats had a 200-μl injection of either autologous blood or saline into the right lateral ventricle and were euthanized at different time points. Rats had magnetic resonance imaging and brains were used for Western blot analysis, immunohistochemistry, histology and brain tissue non-heme iron measurements. Second, rats had IVH and were treated with deferoxamine (DFX) or vehicle, and rats were euthanized 4 weeks later for brain tissue loss and lateral ventricle size measurements. IVH resulted in brain iron accumulation, bilateral enlargement of the lateral ventricles and hippocampal brain tissue loss. Iron accumulation was associated with upregulation of heme oxygenase-1 and ferritin. Systemic DFX treatment reduced IVH-induced ventricular enlargement (e.g. day 28: 32.7±10.6 vs. 43.8±9.7 mm3 in vehicle-treated group, n=8–9, p<0.05) and hippocampal brain tissue loss (hippocampal volume: 89.0±2.7 vs. 85.2±4.1 mm3 in the vehicle-treated group, p<0.05). Iron has a role in brain injury following IVH. DFX may be a therapy for patients with IVH or intraventricular extension after ICH.