Deferoxamine inhibits microglial activation, attenuates blood-brain barrier disruption, rescues dendritic damage, and improves spatial memory in a mouse model of microhemorrhages
Deferoxamine inhibits microglial activation, attenuates blood-brain barrier disruption, rescues dendritic damage, and improves spatial memory in a mouse model of microhemorrhages
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去铁胺抑制小胶质细胞激活，减轻血脑屏障破坏，挽救树突损伤，并改善微出血小鼠模型的空间记忆
DOI：
10.1111/jnc.13657
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发表时间：
2016-08-01
影响因子：
4.7
通讯作者：
Pei, Zhong
中科院分区：
文献类型：
--
作者：
He, Xiao-fei;Lan, Yue;Pei, Zhong
脑微出血与老年人的认知功能障碍密切相关。铁蓄积在颅内出血的发病机制中起重要作用。去铁胺（DFX）是一种金属螯合剂，可消除铁过载，防止颅内出血时的脑损伤。在这项研究中，DFX对小鼠微出血的保护作用进行了研究。用双光子激光照射C57 BL 6和Thy-1绿色荧光蛋白转基因小鼠的右后顶叶皮质，进行穿通动脉显微血管移植。DFX（100 mg/kg）于微出血诱导后6 h开始给药，以后每12 h给药一次，连续3d。诱导后7天进行水迷宫实验，随后测量血脑屏障通透性、铁沉积、小胶质细胞活化和树突状细胞损伤。激光诱导的右顶叶皮质中的多个微出血明显导致空间记忆破坏、铁沉积、小胶质细胞活化和树突状细胞损伤，这些都被DFX显著减弱，支持靶向铁过载作为治疗选择以及DFX在微出血治疗中的显著潜力。
Cerebral microbleeds are strongly linked to cognitive dysfunction in the elderly. Iron accumulation plays an important role in the pathogenesis of intracranial hemorrhage. Deferoxamine (DFX), a metal chelator, removes iron overload and protects against brain damage in intracranial hemorrhage. In this study, the protective effects of DFX against microhemorrhage were examined in mice. C57BL6 and Thy-1 green fluorescent protein transgenic mice were subjected to perforating artery microhemorrhages on the right posterior parietal cortex using two-photon laser irradiation. DFX (100mg/kg) was administered 6h after microhemorrhage induction, followed by every 12h for three consecutive days. The water maze task was conducted 7days after induction of microhemorrhages, followed by measurement of blood-brain barrier permeability, iron deposition, microglial activation, and dendritic damage. Laser-induced multiple microbleeds in the right parietal cortex clearly led to spatial memory disruption, iron deposits, microglial activation, and dendritic damage, which were significantly attenuated by DFX, supporting the targeting of iron overload as a therapeutic option and the significant potential of DFX in microhemorrhage treatment.