Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA.
Stroke Vasc Neurol. 2016 Jun 24;1(2):37-43. doi: 10.1136/svn-2016-000009. eCollection 2016 Jun.
Our recent studies have shown that blood components, including haemoglobin and iron, contribute to hydrocephalus development and brain injury after intraventricular haemorrhage (IVH). The current study investigated the role of lipocalin 2 (LCN2), a protein involved in iron handling, in the ventricular dilation and neuroinflammation caused by brain injury in a mouse model of IVH.
Female wild-type (WT) C57BL/6 mice and LCN2-deficient (LCN2) mice had an intraventricular injection of haemoglobin, and control mice received an equivalent amount of saline. MRI was performed presurgery and postsurgery to measure ventricular volume and the brains were used for either immunohistochemistry or western blot.
Ventricular dilation was observed in WT mice at 24 h after haemoglobin (25 mg/mL, 20 µL) injection (12.5±2.4 vs 8.6±1.5 mm in the control, p<0.01). Western blotting showed that LCN2 was significantly upregulated in the periventricular area (p<0.01). LCN2 was mainly expressed in astrocytes, whereas the LCN2 receptor was detected in astrocytes, microglia/macrophages and neurons. Haemoglobin-induced ventricle dilation and glia activation were less in LCN2 mice (p<0.01). Injection of high-dose haemoglobin (50 mg/mL) resulted in lower mortality in LCN2 mice (27% vs 86% in WT; p<0.05).
Intraventricular haemoglobin caused LCN2 upregulation and ventricular dilation. Haemoglobin resulted in lower mortality and less ventricular dilation in LCN2 mice. These results suggest that LCN2 has a role in haemoglobin-induced brain injury and may be a therapeutic target for IVH.
我们最近的研究表明，血液成分，包括血红蛋白和铁，有助于脑室内出血（IVH）后脑积水的发展和脑损伤。本研究旨在探讨在 IVH 小鼠模型中，参与铁处理的蛋白——脂联素 2（LCN2）在脑损伤引起的脑室扩张和神经炎症中的作用。
雌性野生型（WT）C57BL/6 小鼠和 LCN2 缺陷（LCN2）小鼠脑室内注射血红蛋白，对照组给予等量生理盐水。术前和术后行 MRI 测量脑室容积，用免疫组织化学或 Western blot 检测脑。
血红蛋白（25mg/mL，20μL）注射后 24 小时，WT 小鼠出现脑室扩张（12.5±2.4 比对照组 8.6±1.5mm，p<0.01）。Western blot 显示，LCN2 在脑室周围区明显上调（p<0.01）。LCN2 主要在星形胶质细胞中表达，而 LCN2 受体则在星形胶质细胞、小胶质细胞/巨噬细胞和神经元中检测到。LCN2 小鼠的血红蛋白诱导脑室扩张和胶质细胞激活减少（p<0.01）。高剂量血红蛋白（50mg/mL）注射可降低 LCN2 小鼠的死亡率（27%比 WT 86%；p<0.05）。
脑室内血红蛋白引起 LCN2 上调和脑室扩张。LCN2 小鼠血红蛋白引起的死亡率较低，脑室扩张较少。这些结果表明，LCN2 在血红蛋白诱导的脑损伤中起作用，可能是 IVH 的治疗靶点。
Zotero 插件
