1Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan; and.
2Department of Neurosurgery, Stanford University, Palo Alto, California.
J Neurosurg. 2023 Nov 10;140(5):1482-1492. doi: 10.3171/2023.8.JNS23667. Print 2024 May 1.
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.
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.
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.
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.
尽管人们对出血后脑积水（PHH）的病理生理学机制尚未完全了解，但最近的数据表明血液成分在其中起着重要作用。本研究旨在了解血清水通道蛋白激活复合物（MAC）在脑室内出血（IVH）后何时被激活，以及 MAC 抑制对 PHH 发展的影响。
本研究由四部分组成。首先，24 只年轻雄性大鼠接受立体定向脑室内自体血或生理盐水注射，分别于出血后第 1、3、7 天进行 MRI 检查。其次，18 只大鼠接受脑室内生理盐水、自体血加 ATA 溶剂或自体血加溶剂注射，分别于出血后第 1、3 天进行 MRI 研究。第三，12 只大鼠接受上述脑室内注射，并在出血后 2 小时进行 MRI 检查。最后，24 只大鼠接受上述脑室内注射，并于出血后第 1、7、14、28 天进行 MRI 研究。MR 图像用于计算脑室容积和铁沉积。采用旷场试验评估功能结果。第 28 天的结果报告为动物基线值的比值，并通过对数转换进行归一化。统计分析包括 Shapiro-Wilk 检验正态性，t 检验和单因素方差分析分别用于 2 组和 3 组连续变量。
MAC 在出血后 1 天即可在血肿内发现，并持续至第 7 天。ATA 给药与 vehicle 相比，在出血后 2 小时时导致的脑室内血肿体积相似。在出血后 1 和 3 天，ATA 给药与 vehicle 相比，导致血肿内的脑室容积明显更小，血肿内的红细胞溶血程度明显更低。ATA 给药与 vehicle 相比，28 天后导致的脑室扩大和室周区铁沉积明显更小。在功能上，ATA 大鼠在 28 天时比 vehicle 大鼠移动速度更快，移动距离更长，休息时间更少。
MAC 在 IVH 后 1 天内被激活，并在血肿内持续存在至第 7 天。MAC 抑制在 IVH 后急性减轻了血凝块内的红细胞溶血和脑室扩大。出血后 1 个月，MAC 抑制减轻了脑室扩大和铁积累，并改善了功能结果。
