Deferoxamine-induced attenuation of brain edema and neurological deficits in a rat model of intracerebral hemorrhage
Deferoxamine-induced attenuation of brain edema and neurological deficits in a rat model of intracerebral hemorrhage
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DOI：
10.3171/jns.2004.100.4.0672
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发表时间：
2004-04-01
影响因子：
4.1
通讯作者：
Xi, GH
中科院分区：
文献类型：
--
作者：
Nakamura, T;Keep, RF;Xi, GH
目的。作者之前进行的研究表明，大脑中铁的积累和氧化应激会导致脑出血（ICH）后继发性脑损伤。在本研究中，作者调查了去铁胺（一种铁螯合剂）是否可以减少 ICH 引起的脑损伤。方法。每只Mate Sprague Dawley大鼠的右侧基底神经节注射100μl自体全血，并在1、3或7天后处死。通过组织化学检查铁分布（增强 Perls 反应）。通过测量脑水肿和神经功能缺损来检查去铁胺对 ICH 引起的脑损伤的影响。采用免疫组织化学分析来研究 DNA 氧化损伤的标志物 8-羟基-2'-脱氧鸟苷 (8-OHdG)，并进行蛋白质印迹分析来测量 DNA 氧化损伤的修复机制脱嘌呤/脱嘧啶核酸内切酶/氧化还原效应因子-1 (APE/Ref-1) 的量。从 ICH 后第 1 天起，在血肿周围区域观察到铁积累。去铁胺可减轻脑水肿、神经功能缺损以及 ICH 引起的 8-OHdG 和 APE/Ref-1 变化。结论。去铁胺和其他铁螯合剂可能是脑出血的潜在治疗剂。它们可能通过减少血肿释放铁引起的氧化应激来发挥作用。
Object. Previous Studies undertaken by the authors have indicated that iron accumulation and oxidative stress in the brain contribute to secondary brain damage after intracerebral hemorrhage (ICH). In the present study the authors investigate whether deferoxamine, an iron chelator, can reduce ICH-induced brain injury.Methods. Mate Sprague Dawley rats each received an infusion of 100 mul of autologous whole blood into the right basal ganglia and were killed 1, 3, or 7 days later. Iron distribution was examined histochemically (enhanced Perls reaction). The effects of deferoxamine on ICH-induced brain injury were examined by measuring brain edema and neurological deficits. Immunohistochemical analysis was performed to investigate 8-hydroxyl-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, and Western blot analysis was performed to measure the amount of apurinic/apyrimidinic endonuclease/redox effector factor-1 (APE/Ref-1), a repair mechanism for DNA oxidative damage.Iron accumulation was observed in the perihematomal zone from I day after ICH. Deferoxamine attenuated brain edema, neurological deficits, and ICH-induced changes in 8-OHdG and APE/Ref-1.Conclusions. Deferoxamine and other iron chelators may be potential therapeutic agents for ICH. They may act by reducing the oxidative stress caused by the release of iron from the hematoma.