OBJECTIVE The pathophysiology of posthemorrhagic hydrocephalus (PHH) is not well understood, but recent data suggest blood components play a significant role. This study aimed to understand the timing of membrane attack complex (MAC) activation after intraventricular hemorrhage (IVH) and the effect of MAC inhibition on PHH development. METHODS This study was composed of four parts. First, 24 young adult male rats underwent stereotactic intraventricular injection of autologous blood or saline and MRI on day 1, 3, or 7 after hemorrhage. Second, 18 rats underwent intraventricular injection of saline, autologous blood with aurin tricarboxylic acid (ATA) in vehicle, or autologous blood with vehicle and underwent serial MRI studies on days 1 and 3 after hemorrhage. Third, 12 rats underwent intraventricular injections as above and MRI 2 hours after hemorrhage. Finally, 24 rats underwent the intraventricular injections as above, as well as serial MRI studies on days 1, 7, 14, and 28 after hemorrhage. The MR images were used to calculate ventricular volume and iron deposition. Open field testing was performed to assess functional outcomes. Outcomes on day 28 were reported as a ratio to the animal's baseline values and normalized via log-transformation. Statistical analysis included the Shapiro-Wilk tests for normality and t-tests and 1-way analysis of variance for 2 and 3 groups of continuous variables, respectively. RESULTS MAC was found within the hematoma 1 day after hemorrhage and persisted until day 7. Administration of ATA resulted in similar intraventricular hematoma volumes compared to vehicle 2 hours after hemorrhage. At 1 and 3 days after hemorrhage, ATA administration resulted in significantly smaller ventricular volumes and less hemolysis within the hematoma than in the vehicle animals. Administration of ATA also resulted in significantly smaller ventriculomegaly and less iron deposition in the periventricular area than in the vehicle rats 28 days after hemorrhage. Functionally, ATA rats were significantly faster, traveled longer distances, and spent less time resting than vehicle rats at 28 days. CONCLUSIONS MAC was activated early and persisted within the hematoma until day 7 after IVH. MAC inhibition attenuated hemolysis in the clot and ventriculomegaly acutely after IVH. One month after hemorrhage, MAC inhibition attenuated ventriculomegaly and iron accumulation and improved functional outcomes.

中文翻译：

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通过膜攻击复合物抑制减轻脑室内出血后脑室扩大和铁超负荷。

目的 出血后脑积水 (PHH) 的病理生理学尚不清楚，但最近的数据表明血液成分发挥着重要作用。本研究旨在了解脑室内出血 (IVH) 后膜攻击复合物 (MAC) 激活的时间以及 MAC 抑制对 PHH 发展的影响。方法本研究由四部分组成。首先，24只年轻成年雄性大鼠在出血后第1、3或7天接受立体定向脑室内注射自体血液或盐水并进行MRI。其次，18 只大鼠接受了脑室内注射生理盐水、含有金精三羧酸 (ATA) 的自体血液或含有载体的自体血液，并在出血后第 1 天和第 3 天进行了系列 MRI 研究。第三，12只大鼠在出血后2小时接受上述脑室内注射和MRI。最后，24只大鼠接受上述脑室内注射，并在出血后第1、7、14和28天进行系列MRI研究。MR 图像用于计算心室体积和铁沉积。进行旷场测试以评估功能结果。第 28 天的结果以与动物基线值的比率报告，并通过对数转换标准化。统计分析包括分别对 2 组和 3 组连续变量进行正态性的 Shapiro-Wilk 检验和 t 检验以及单向方差分析。结果 出血后 1 天在血肿内发现 MAC，并持续到第 7 天。出血后 2 小时，与载体相比，给予 ATA 导致相似的脑室内血肿体积。出血后第 1 天和第 3 天，与载体动物相比，给予 ATA 导致心室体积显着减小，血肿内溶血也减少。出血后28天，与载体大鼠相比，给予ATA还导致脑室扩大明显缩小，脑室周围区域铁沉积减少。从功能上来说，28 天时，ATA 大鼠比媒介鼠明显更快、移动距离更长、休息时间更少。结论 MAC 早期被激活并在血肿内持续存在直至 IVH 后第 7 天。MAC 抑制可显着减轻 IVH 后血栓中的溶血和脑室扩大。出血后一个月，MAC 抑制减轻了脑室扩大和铁积累，并改善了功能结果。