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Iron accumulation in the choroid plexus, ependymal cells and CNS parenchyma in a rat strain with low‐grade haemolysis of fragile macrocytic red blood cells
Brain Pathology ( IF 5.8 ) Pub Date : 2020-11-21 , DOI: 10.1111/bpa.12920 Isabella Wimmer 1, 2 , Cornelia Scharler 2 , Taro Kadowaki 2, 3 , Sophie Hillebrand 2 , Barbara Scheiber-Mojdehkar 4 , Shuichi Ueda 5 , Monika Bradl 2 , Thomas Berger 1 , Hans Lassmann 2 , Simon Hametner 2, 6
Brain Pathology ( IF 5.8 ) Pub Date : 2020-11-21 , DOI: 10.1111/bpa.12920 Isabella Wimmer 1, 2 , Cornelia Scharler 2 , Taro Kadowaki 2, 3 , Sophie Hillebrand 2 , Barbara Scheiber-Mojdehkar 4 , Shuichi Ueda 5 , Monika Bradl 2 , Thomas Berger 1 , Hans Lassmann 2 , Simon Hametner 2, 6
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Iron accumulation in the CNS is associated with many neurological diseases via amplification of inflammation and neurodegeneration. However, experimental studies on iron overload are challenging, since rodents hardly accumulate brain iron in contrast to humans. Here, we studied LEWzizi rats, which present with elevated CNS iron loads, aiming to characterise choroid plexus, ependymal, CSF and CNS parenchymal iron loads in conjunction with altered blood iron parameters and, thus, signifying non‐classical entry sites for iron into the CNS. Non‐haem iron in formalin‐fixed paraffin‐embedded tissue was detected via DAB‐enhanced Turnbull Blue stainings. CSF iron levels were determined via atomic absorption spectroscopy. Ferroportin and aquaporin‐1 expression was visualised using immunohistochemistry. The analysis of red blood cell indices and serum/plasma parameters was based on automated measurements; the fragility of red blood cells was manually determined by the osmotic challenge. Compared with wild‐type animals, LEWzizi rats showed strongly increased iron accumulation in choroid plexus epithelial cells as well as in ependymal cells of the ventricle lining. Concurrently, red blood cell macrocytosis, low‐grade haemolysis and significant haemoglobin liberation from red blood cells were apparent in the peripheral blood of LEWzizi rats. Interestingly, elevated iron accumulation was also evident in kidney proximal tubules, which share similarities with the blood–CSF barrier. Our data underscore the importance of iron gateways into the CNS other than the classical route across microvessels in the CNS parenchyma. Our findings of pronounced choroid plexus iron overload in conjunction with peripheral iron overload and increased RBC fragility in LEWzizi rats may be seminal for future studies of human diseases, in which similar constellations are found.
中文翻译：
铁在脉络丛、室管膜细胞和中枢神经系统实质中的积累
通过炎症和神经变性的放大，中枢神经系统中的铁积累与许多神经系统疾病有关。然而，关于铁过载的实验研究具有挑战性，因为与人类相比，啮齿动物几乎不会积累脑铁。在这里，我们研究了中枢神经系统铁负荷升高的 LEWzizi 大鼠，旨在结合血铁参数改变来表征脉络丛、室管膜、脑脊液和中枢神经系统实质铁负荷，从而表明铁进入大脑的非经典进入位点。中枢神经系统。通过 DAB 增强的特恩布尔蓝染色检测福尔马林固定石蜡包埋组织中的非血红素铁。CSF 铁水平通过原子吸收光谱法测定。使用免疫组织化学可视化铁转运蛋白和水通道蛋白-1 的表达。红细胞指数和血清/血浆参数的分析基于自动测量；红细胞的脆性是通过渗透挑战手动确定的。与野生型动物相比，LEWzizi 大鼠的脉络丛上皮细胞以及心室衬里的室管膜细胞中的铁积累显着增加。同时，LEWzizi 大鼠外周血中红细胞巨细胞增多症、低度溶血和红细胞中显着的血红蛋白释放是明显的。有趣的是，在肾近端小管中也有明显的铁积累，这与血液-脑脊液屏障有相似之处。我们的数据强调了铁通道进入 CNS 的重要性，而不是穿过 CNS 实质中微血管的经典途径。
更新日期：2020-11-21
中文翻译：
铁在脉络丛、室管膜细胞和中枢神经系统实质中的积累
通过炎症和神经变性的放大，中枢神经系统中的铁积累与许多神经系统疾病有关。然而，关于铁过载的实验研究具有挑战性，因为与人类相比，啮齿动物几乎不会积累脑铁。在这里，我们研究了中枢神经系统铁负荷升高的 LEWzizi 大鼠，旨在结合血铁参数改变来表征脉络丛、室管膜、脑脊液和中枢神经系统实质铁负荷，从而表明铁进入大脑的非经典进入位点。中枢神经系统。通过 DAB 增强的特恩布尔蓝染色检测福尔马林固定石蜡包埋组织中的非血红素铁。CSF 铁水平通过原子吸收光谱法测定。使用免疫组织化学可视化铁转运蛋白和水通道蛋白-1 的表达。红细胞指数和血清/血浆参数的分析基于自动测量；红细胞的脆性是通过渗透挑战手动确定的。与野生型动物相比，LEWzizi 大鼠的脉络丛上皮细胞以及心室衬里的室管膜细胞中的铁积累显着增加。同时，LEWzizi 大鼠外周血中红细胞巨细胞增多症、低度溶血和红细胞中显着的血红蛋白释放是明显的。有趣的是，在肾近端小管中也有明显的铁积累，这与血液-脑脊液屏障有相似之处。我们的数据强调了铁通道进入 CNS 的重要性，而不是穿过 CNS 实质中微血管的经典途径。
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