Nakamura Takehiro, Keep Richard F, Hua Ya, Schallert Timothy, Hoff Julian T, Xi Guohua
Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan 48109-0532, USA.
Neurosurg Focus. 2003 Oct 15;15(4):ECP4. doi: 10.3171/foc.2003.15.4.10.
In the authors' previous studies they found that brain iron accumulation and oxidative stress contribute to secondary brain damage after intracerebral hemorrhage (ICH). In the present study they investigated whether deferoxamine, an iron chelator, can reduce ICH-induced brain injury.
Male Sprague-Dawley rats received an infusion of 100 microl of autologous whole blood into the right basal ganglia and were killed 1, 3, or 7 days thereafter. Iron distribution was examined histochemically (enhanced Perl reaction). The effects of deferoxamine on ICH-induced brain injury were examined by measuring brain edema and neurological deficits. Apurinic/apyrimidinic endonuclease/redox effector factor-1 (APE/Ref-1), a repair mechanism for DNA oxidative damage, was quantitated by Western blot analysis. Iron accumulation was observed in the perihematoma zone beginning 1 day after ICH. Deferoxamine attenuated brain edema, neurological deficits, and ICH-induced changes in APE/Ref-1.
Deferoxamine and other iron chelators may be potential therapeutic agents for treating ICH. They may act by reducing the oxidative stress caused by the release of iron from the hematoma.
在作者之前的研究中，他们发现脑铁蓄积和氧化应激会导致脑出血（ICH）后的继发性脑损伤。在本研究中，他们调查了铁螯合剂去铁胺是否能减轻ICH诱导的脑损伤。
雄性Sprague-Dawley大鼠右侧基底节区注入100微升自体全血，然后在1、3或7天后处死。通过组织化学方法（增强的Perl反应）检测铁分布。通过测量脑水肿和神经功能缺损来检查去铁胺对ICH诱导的脑损伤的影响。通过蛋白质印迹分析对DNA氧化损伤的修复机制——脱嘌呤/脱嘧啶内切酶/氧化还原效应因子-1（APE/Ref-1）进行定量。ICH后1天开始在血肿周围区域观察到铁蓄积。去铁胺减轻了脑水肿、神经功能缺损以及ICH诱导的APE/Ref-1变化。
去铁胺和其他铁螯合剂可能是治疗ICH的潜在治疗药物。它们可能通过减少血肿中铁释放引起的氧化应激而起作用。
