Department of Neurosurgery, University of Michigan, Ann Arbor, Mich 48109-2200, USA.
Stroke. 2010 Feb;41(2):375-82. doi: 10.1161/STROKEAHA.109.569830. Epub 2009 Dec 31.
Deferoxamine (DFX) reduces brain edema, neurological deficits, and brain atrophy after intracerebral hemorrhage (ICH) in aged and 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 months old) sustained an intracaudate injection of 100 microL autologous whole blood, followed by intramuscular DFX or vehicle beginning at different time points, or continuing for different durations. Subgroups of rats were euthanized at day 3 for brain edema measurement and day 56 for brain atrophy determination. Behavioral tests were performed on days 1, 28, and 56 after 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 >or=7 days 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.
去铁胺（DFX）可减轻脑出血（ICH）后老龄和年轻大鼠的脑水肿、神经功能缺损和脑萎缩。我们之前的研究发现 50mg/kg 是老龄大鼠的有效剂量。在本研究中，我们探索了潜在的治疗时间窗和最佳治疗持续时间。
雄性老龄 Fischer 344 大鼠（18 个月龄）接受尾状核内 100μL 自体全血注射，随后在不同时间点开始肌肉内给予 DFX 或载体，或持续不同时间。亚组大鼠于第 3 天处死，用于脑水肿测量，第 56 天处死，用于脑萎缩测定。ICH 后第 1、28 和 56 天进行行为学测试。
ICH 后 12 小时内开始全身给予 DFX 可减轻脑水肿。ICH 后 2 小时开始治疗并持续 >或=7 天可减轻 ICH 引起的脑室扩大、尾状核萎缩和神经功能缺损。ICH 后 24 小时内开始并持续 7 天给予 DFX 可减轻 ICH 引起的脑萎缩和神经功能缺损，且无明显副作用。
在一定程度上，这些结果可转化为人类，DFX 在该 ICH 老龄大鼠模型中的治疗时间窗和最佳持续时间可能为正在进行的 DFX-ICH 临床试验提供有用信息。
