Quantification of different iron forms in the aceruloplasminemia brain to explore iron-related neurodegeneration.
Quantification of different iron forms in the aceruloplasminemia brain to explore iron-related neurodegeneration.
复制标题
DOI：
10.1016/j.nicl.2021.102657
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Langendonk JG
中科院分区：
文献类型：
--
作者：
Vroegindeweij LHP;Bossoni L;Boon AJW;Wilson JHP;Bulk M;Labra-Muñoz J;Huber M;Webb A;van der Weerd L;Langendonk JG
铁水合铁是急性纤溶酶血症患者大脑中最丰富的铁形式。在深部灰质结构中发现铁浓度超过1mg /g。深灰质的铁含量是颞叶皮层的三倍多。铁敏感的MRI对比主要是由铁水合铁的数量驱动的。R2*比7 t时的QSM更能说明铁积累的模式。酸紫浆蛋白血症是一种与大量脑铁沉积相关的超罕见神经退行性疾病，其分子组成尚不清楚。我们的目的是定量地确定尖纤溶酶血症脑中的分子铁形式，并说明它们对铁敏感的MRI指标的影响。利用电子顺磁共振（EPR）和超导量子干涉器件（SQUID）磁强计，结合7 T MRI得到的非均匀横向弛豫率（R2*）和磁化率。研究了死后急性纤溶酶血症脑的基底神经节、丘脑、红核、齿状核、颞上回和中回以及白质。健康对照的颞叶皮层MRI、EPR和SQUID结果被纳入比较。本研究检测的急性纤溶酶血症患者脑铁池由epr可检测的Fe3+离子、嵌入铁蛋白和含铁血黄素核心的磁性Fe3+离子（铁水合铁）和嵌入氧化磁铁矿/磁铁矿矿物中的磁性Fe3+离子（磁铁矿-铁）组成。铁水合铁占所有铁的90%以上，是铁敏感MRI对比的主要驱动因素。尽管深灰质结构中水合铁的含量是颞叶皮层的3倍，但与健康情况相比，急性纤溶酶血症患者颞叶皮层中的水合铁含量已经高出6倍（平均162 μ g/g vs 27 μ g/g）。尖珠纤溶酶血症患者颞叶皮层中Fe3+离子和磁铁矿铁浓度与对照组基本一致。铁相关性神经退行性变主要与铁水合铁增加有关，铁水合铁是铁敏感MRI对比的主要决定因素。
Ferrihydrite-iron is the most abundant iron form in the aceruloplasminemia brain. Iron concentrations over 1 mg/g are found in deep gray matter structures. The deep gray matter contains over three times more iron than the temporal cortex. Iron-sensitive MRI contrast is primarily driven by the amount of ferrihydrite-iron. R2* is more illustrative of the pattern of iron accumulation than QSM at 7 T. Aceruloplasminemia is an ultra-rare neurodegenerative disorder associated with massive brain iron deposits, of which the molecular composition is unknown. We aimed to quantitatively determine the molecular iron forms in the aceruloplasminemia brain, and to illustrate their influence on iron-sensitive MRI metrics. The inhomogeneous transverse relaxation rate (R2*) and magnetic susceptibility obtained from 7 T MRI were combined with Electron Paramagnetic Resonance (EPR) and Superconducting Quantum Interference Device (SQUID) magnetometry. The basal ganglia, thalamus, red nucleus, dentate nucleus, superior- and middle temporal gyrus and white matter of a post-mortem aceruloplasminemia brain were studied. MRI, EPR and SQUID results that had been previously obtained from the temporal cortex of healthy controls were included for comparison. The brain iron pool in aceruloplasminemia detected in this study consisted of EPR-detectable Fe3+ ions, magnetic Fe3+ embedded in the core of ferritin and hemosiderin (ferrihydrite-iron), and magnetic Fe3+ embedded in oxidized magnetite/maghemite minerals (maghemite-iron). Ferrihydrite-iron represented above 90% of all iron and was the main driver of iron-sensitive MRI contrast. Although deep gray matter structures were three times richer in ferrihydrite-iron than the temporal cortex, ferrihydrite-iron was already six times more abundant in the temporal cortex of the patient with aceruloplasminemia compared to the healthy situation (162 µg/g vs. 27 µg/g), on average. The concentrations of Fe3+ ions and maghemite-iron in the temporal cortex in aceruloplasminemia were within the range of those in the control subjects. Iron-related neurodegeneration in aceruloplasminemia is primarily associated with an increase in ferrihydrite-iron, with ferrihydrite-iron being the major determinant of iron-sensitive MRI contrast.
登录
查看更多内容
影响因子：
5.8
作者：
Hagemeier, Jesper;Yeh, E. Ann;Zivadinov, Robert
通讯作者：
Zivadinov, Robert
影响因子：
3.3
作者：
Colgan, Timothy J.;Knobloch, Gesine;Hernando, Diego
通讯作者：
Hernando, Diego
影响因子：
11
作者：
Kawanami, T;Kato, T;Katagiri, T
通讯作者：
Katagiri, T
影响因子：
2.6
作者：
Kalyanaraman B;Cheng G;Zielonka J;Bennett B
通讯作者：
Bennett B
影响因子：
3.3
作者：
Jensen, Jens H.;Tang, Haiying;Brittenham, Gary M.
通讯作者：
Brittenham, Gary M.