Deferoxamine treatment for intracerebral hemorrhage in aged rats: therapeutic time window and optimal duration.
Deferoxamine treatment for intracerebral hemorrhage in aged rats: therapeutic time window and optimal duration.
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DOI：
10.1161/strokeaha.109.569830
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发表时间：
2010-02
期刊：
影响因子：
8.3
通讯作者：
Xi G
中科院分区：
文献类型：
--
作者：
Okauchi M;Hua Y;Keep RF;Morgenstern LB;Schallert T;Xi G
去铁胺（DFX）可减轻老年和青年大鼠脑出血（ICH）后的脑水肿、神经功能缺损和脑萎缩。我们以前的研究发现，50 mg/kg是老年大鼠的有效剂量。在本研究中，我们探讨了潜在的治疗时间窗和最佳治疗持续时间。老年雄性Fischer 344大鼠（18月龄）持续尾状核内注射100 µL自体全血，然后在不同时间点开始肌内注射DFX或溶媒，或持续不同的持续时间。在第3天处死大鼠亚组用于脑水肿测量，在第56天处死大鼠亚组用于脑萎缩测定。在ICH后第1、28和56天进行行为测试。在ICH后12小时内开始全身给予DFX可减轻脑水肿。DFX治疗在ICH后2小时开始，给药7天或更长时间，可减轻ICH诱导的脑室扩大、尾状核萎缩和神经功能缺损。DFX在24小时内开始给药7天后，可减轻ICH诱导的脑萎缩和神经功能缺损，且无可检测到的副作用。在一定程度上，这些结果可以转化为人类，治疗时间窗和最佳持续时间的DFX在这个老年大鼠模型的ICH可能提供有用的信息，为正在进行的DFX-ICH临床试验。
Deferoxamine (DFX) reduces brain edema, neurological deficits and brain atrophy after intracerebral hemorrhage (ICH) in aged as well as young rats. Our previous study found that 50 mg/kg is an effective dose in aged rats. In the present study, we explored potential therapeutic time windows and optimal therapeutic durations. Aged male Fischer 344 rats (18-month old) sustained an intra-caudate injection of 100-µL autologous whole blood, followed by intramuscular DFX or vehicle beginning at different time points, or continuing for different durations. Subgroups of rats were sacrificed at day 3 for brain edema measurement and day 56 for brain atrophy determination. Behavioral tests were carried out on days 1, 28 and 56 post-ICH. Systemic administration of DFX, when begun within 12 hours after ICH, reduced brain edema. DFX treatment started 2 hours after ICH and administered for 7 days or more attenuated ICH-induced ventricle enlargement, caudate atrophy and neurological deficits. DFX attenuated ICH-induced brain atrophy and neurological deficits without detectable side effects when begun within 24 hours and administered for 7 days. To the extent that these results can be translated to humans, the therapeutic time window and the optimal duration for DFX in this aged rat model of ICH may provide useful information for an ongoing DFX-ICH clinical trial.