Spatial-temporal changes of iron deposition and iron metabolism after traumatic brain injury in mice.
Spatial-temporal changes of iron deposition and iron metabolism after traumatic brain injury in mice.
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小鼠脑外伤后铁沉积和铁代谢的时空变化
DOI：
10.3389/fnmol.2022.949573
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发表时间：
2022
影响因子：
4.8
通讯作者：
Zhao, Rui
中科院分区：
文献类型：
--
作者：
Cheng, Hao;Wang, Ning;Ma, Xingyu;Wang, Pengfei;Dong, Wenwen;Chen, Ziyuan;Wu, Mingzhe;Wang, Ziwei;Wang, Linlin;Guan, Dawei;Zhao, Rui
关键词：
血红蛋白和坏死组织释放过量铁是加重创伤性脑损伤（TBI）预后的主要因素。调节铁的水平及其代谢是减轻创伤性脑损伤的可行方法。然而，脑外伤后神经元和神经胶质细胞的铁代谢和铁沉积的时空变化尚不清楚。在我们的研究中，雄性C57BL/6小鼠（8-12周龄，体重20-26 g）采用控制性皮质冲击（CCI）模型，结合铁螯合剂去铁胺（DFO）治疗，系统评估铁沉积、铁代谢蛋白的细胞特异性表达和同侧皮质铁下沉。本研究发现，同侧皮质出现铁超载和脂质过氧化导致的铁下垂。此外，损伤后1-3天，在同侧皮质神经元中观察到铁沉积和铁代谢蛋白的细胞特异性表达。然而，星形胶质细胞中没有铁超载，即使它们有强烈的tbi诱导的氧化应激。此外，少突胶质细胞中的铁积累仅在损伤后7-14天观察到，这与细胞修复的相应间隔时间一致。小胶质细胞在脑外伤后铁的吞噬和代谢中发挥重要作用，过量影响小胶质细胞M1和M2亚型的转化和激活。我们的研究表明，脑外伤导致同侧皮质铁下沉，脑外伤后神经元和神经胶质细胞的铁沉积和代谢表现出细胞类型特异性的时空变化。神经元和神经胶质细胞铁沉积和铁代谢的不同作用和动态变化，有助于为改善TBI治疗提供铁代谢机制和策略的新见解。
Excessive iron released by hemoglobin and necrotic tissues is the predominant factor that aggravates the outcome of traumatic brain injury (TBI). Regulating the levels of iron and its metabolism is a feasible way to alleviate damage due to TBI. However, the spatial-temporal iron metabolism and iron deposition in neurons and glial cells after TBI remains unclear. In our study, male C57BL/6 mice (8–12 weeks old, weighing 20–26 g) were conducted using controlled cortical impact (CCI) models, combined with treatment of iron chelator deferoxamine (DFO), followed by systematical evaluation on iron deposition, cell-specific expression of iron metabolic proteins and ferroptosis in ipsilateral cortex. Herein, ferroptosis manifest by iron overload and lipid peroxidation was noticed in ipsilateral cortex. Furthermore, iron deposition and cell-specific expression of iron metabolic proteins were observed in the ipsilateral cortical neurons at 1–3 days post-injury. However, iron overload was absent in astrocytes, even though they had intense TBI-induced oxidative stress. In addition, iron accumulation in oligodendrocytes was only observed at 7–14 days post-injury, which was in accordance with the corresponding interval of cellular repair. Microglia play significant roles in iron engulfment and metabolism after TBI, and excessive affects the transformation of M1 and M2 subtypes and activation of microglial cells. Our study revealed that TBI led to ferroptosis in ipsilateral cortex, iron deposition and metabolism exhibited cell-type-specific spatial-temporal changes in neurons and glial cells after TBI. The different effects and dynamic changes in iron deposition and iron metabolism in neurons and glial cells are conducive to providing new insights into the iron-metabolic mechanism and strategies for improving the treatment of TBI.
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影响因子：
11.4
作者：
Feng Z;Min L;Chen H;Deng W;Tan M;Liu H;Hou J
通讯作者：
Hou J
影响因子：
8
作者：
Andersen, Hjalte Holm;Johnsen, Kasper Bendix;Moos, Torben
通讯作者：
Moos, Torben
铁转运蛋白的缺失会通过促进阿尔茨海默病中的铁死亡而导致记忆障碍。
影响因子：
12.4
作者：
Bao WD;Pang P;Zhou XT;Hu F;Xiong W;Chen K;Wang J;Wang F;Xie D;Hu YZ;Han ZT;Zhang HH;Wang WX;Nelson PT;Chen JG;Lu Y;Man HY;Liu D;Zhu LQ
通讯作者：
Zhu LQ
DOI：
10.1007/978-3-7091-0693-8_20
发表时间：
2011-01-01
期刊：
INTRACEREBRAL HEMORRHAGE RESEARCH: FROM BENCH TO BEDSIDE
影响因子：
--
作者：
Gu, Yuxiang;Hua, Ya;Xi, Guohua
通讯作者：
Xi, Guohua
DOI：
10.1073/pnas.95.3.1148
发表时间：
1998-02-03
影响因子：
11.1
作者：
Fleming, MD;Romano, MA;Andrews, NC
通讯作者：
Andrews, NC