Failure of deferoxamine, an iron chelator, to improve outcome after collagenase-induced intracerebral hemorrhage in rats
Failure of deferoxamine, an iron chelator, to improve outcome after collagenase-induced intracerebral hemorrhage in rats
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DOI：
10.1016/j.brainres.2009.10.058
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发表时间：
2010-01-14
期刊：
影响因子：
2.9
通讯作者：
Colbourne, Frederick
中科院分区：
文献类型：
--
作者：
Warkentin, Lindsey M.;Auriat, Angela M.;Colbourne, Frederick
脑出血 (ICH) 是一种毁灭性中风，尚无经过临床证明的治疗方法。去铁胺 (DFX) 是一种铁螯合剂，是一种有前景的疗法，可减轻啮齿类动物全血诱发的脑出血后的水肿、减轻血肿周围细胞死亡并改善行为恢复。在该模型中，血液直接注入大脑，通常注入纹状体。这模仿了 ICH 的许多但不是全部临床特征（例如，没有自发出血）。因此，我们测试了 DFX 是否可以改善胶原酶诱导的大鼠纹状体 ICH 后的结果。在第一个实验中，将 3 天和 7 天的 DFX 方案（ICH 后 6 小时开始，每天两次，每次 100 mg/kg）与盐水治疗进行了比较，该方案与在全血模型中显示有效的方案类似。通过多项行为测试评估 3 至 28 天的功能恢复情况。除了一个例子外，DFX 未能减轻 ICH 引起的行为障碍，也没有减轻脑损伤，28 天生存期的脑损伤平均为 43.5 mm(3)。在第二个实验中，在胶原酶输注后 0 或 6 小时开始进行 3 天的 DFX 治疗。纹状体水肿发生，但不受任一 DFX 治疗（与盐水治疗）的影响。因此，与使用全血模型的研究相比，DFX 治疗并没有改善胶原酶模型的结果。与其他模型相比，我们的研究结果表明这些 ICH 模型之间存在重大差异。也许，目前 DFX 的临床工作将有助于确定未来神经保护更具临床预测性的模型。研究。 (C) 2009 Elsevier B.V. 保留所有权利。
Intracerebral hemorrhage (ICH) is a devastating stroke with no clinically proven treatment. Deferoxamine (DFX), an iron chelator, is a promising therapy that lessens edema, mitigates peri-hematoma cell death, and improves behavioral recovery after whole-blood-induced ICH in rodents. In this model, blood is directly injected into the brain, usually into the striatum. This mimics many but not all clinical features of ICH (e.g., there is no spontaneous bleed). Thus, we tested whether DFX improves outcome after collagenase-induced striatal ICH in rats. In the first experiment, 3- and 7-day DFX regimens (100 mg/kg twice per day starting 6 h after ICH), similar to those shown effective in the whole-blood model, were compared to saline treatment. Functional recovery was evaluated from 3 to 28 days with several behavioral tests. Except for one instance, DFX failed to lessen ICH-induced behavioral impairments and it did not lessen brain injury, which averaged 43.5 mm(3) at a 28-day survival. In the second experiment, 3 days of DFX treatment were given starting 0 or 6 h after collagenase infusion. Striatal edema occurred, but it was not affected by either DFX treatment (vs. saline treatment). Therefore, in contrast to studies using the whole-blood model, DFX treatment did not improve outcome in the collagenase model. Our findings, when compared to others, suggest that there are critical differences between these ICH models. Perhaps, the current clinical work with DFX will help identify the more clinically predictive model for future neuroprotection. studies. (C) 2009 Elsevier B.V. All rights reserved.