Okauchi Masanobu, Hua Ya, Keep Richard F, Morgenstern Lewis B, Xi Guohua
Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan 48109-2200, USA.
Stroke. 2009 May;40(5):1858-63. doi: 10.1161/STROKEAHA.108.535765. Epub 2009 Mar 12.
Deferoxamine (DFX) reduces brain edema, neuronal death, and neurological deficits after intracerebral hemorrhage (ICH) in young rats. In the present study, we investigated whether DFX is effective on brain injury after ICH in aged rats and examined dose dependency.
Male Fischer 344 rats (18 months old) had an intracaudate injection of 100 microL autologous whole blood and were treated with different doses of DFX (10, 50, and 100 mg/kg) or vehicle 2 and 6 hours post-ICH and then every 12 hours up to 7 days. Rats were euthanized at Day 3 for brain edema determination and Day 56 for brain atrophy measurement. Behavioral tests were performed during the experiments.
All 3 doses of DFX attenuated perihematomal brain edema at 3 days (eg, at dose 50 mg/kg, 80.4+/-0.5 versus 81.6+/-0.9% in the vehicle-treated group, P<0.01). Fifty and 100 mg/kg DFX also reduced ICH-induced ventricle enlargement, caudate atrophy, and ICH-induced neurological deficits in aged rats. However, although 10 mg/kg DFX reduced ventricle enlargement and forelimb-placing deficits, it did not reduce caudate atrophy and corner turn deficits.
These results indicate that DFX can reduce ICH-induced brain injury in aged as well as young rats and that a dose >10 mg/kg is the optimal dose of DFX in this model.
去铁胺（DFX）可减轻年轻大鼠脑出血（ICH）后的脑水肿、神经元死亡及神经功能缺损。在本研究中，我们调查了DFX对老年大鼠ICH后脑损伤是否有效，并研究了剂量依赖性。
雄性Fischer 344大鼠（18月龄）尾状核内注射100 μL自体全血，在ICH后2小时和6小时用不同剂量的DFX（10、50和100 mg/kg）或溶剂进行治疗，然后每12小时给药一次，持续7天。在第3天对大鼠实施安乐死以测定脑水肿，在第56天测定脑萎缩。实验期间进行行为测试。
所有3个剂量的DFX均在第3天减轻了血肿周围脑水肿（例如，50 mg/kg剂量组，为80.4±0.5%，而溶剂治疗组为81.6±0.9%，P<0.01）。50和100 mg/kg的DFX还减少了老年大鼠ICH引起的脑室扩大、尾状核萎缩及ICH引起的神经功能缺损。然而，尽管10 mg/kg的DFX减少了脑室扩大和前肢放置缺陷，但并未减少尾状核萎缩和转角缺陷。
这些结果表明，DFX可减轻老年和年轻大鼠ICH引起的脑损伤，且在该模型中，剂量>10 mg/kg是DFX的最佳剂量。
