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Effect Comparison of Both Iron Chelators on Outcomes, Iron Deposit, and Iron Transporters After Intracerebral Hemorrhage in Rats

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Abstract

Iron overload plays a key role in brain injury after intracerebral hemorrhage (ICH). We explored the roles of ferric iron chelator—deferiprone (DFP)—and ferrous iron chelator—clioquinol (CQ)—in ICH rats through the outcomes, iron deposits, reactive oxygen species (ROS), brain water content, and related iron transporters. One hundred eight Sprague-Dawley rats received intra-striatal infusions of 0.5 U of type IV collagenase to establish ICH models. The rats were randomly assigned to the sham, vehicle, DFP, and CQ groups. We evaluated the outcomes, iron levels, brain water content, and ROS; meanwhile, immunohistochemistry and real-time quantitative polymerase chain reaction (RT-qPCR) were utilized to determine ferritin, transferrin, transferrin receptor, divalent metal transport 1 (DMT1), and ferroportin at 48 and 72 h, 7 and 14 days after surgery. Our results showed ICH induced iron overload, brain edema, ROS formation, and neurological deficits. Both iron chelators decreased iron levels; CQ improved the neurological outcome, attenuated brain edema, and ROS production. DFP reduced iron contents but not brain water content and ROS generation. DFP failed to improve the outcome. ICH initiated endogenous iron chelators and transporters, both exogenous iron chelators enhanced expression of transferrin and transferrin receptor. CQ enhanced expression of ferroportin but not DMT1, while DFP enhanced expression of DMT1 but not ferroportin. Ferrous iron contributed to brain injury, and binding ferrous iron can modestly improve outcome after ICH in rats. The exogenous ferrous iron chelator possibly functioned via endogenous ferrous iron transporters on ICH. Therefore, ferrous iron may be a promising target for ICH in future.

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Acknowledgments

This work was supported by the Shanxi provincial Science and Technology Agency (2014011041-5) and Shanxi provincial Hygiene Department (201301010).

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Authors and Affiliations

  1. Department of Neurology, the Second Hospital, Shanxi Medical University, 382 Wuyi Avenue, Taiyuan, Shanxi, 030001, China

    Gaiqing Wang, Weimin Hu, Li Wang, Xin-gang Sun, Yanli Chen, Yongfeng Yin, Fang Xue & Zhitang Sun

  2. Department of Rehabilitation, Brain Hospital of Hunan Province, 2427 Furong Middle Road, Changsha, Hunan, 410007, China

    Qingping Tang

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  1. Gaiqing Wang
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Correspondence to Gaiqing Wang.

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Wang, G., Hu, W., Tang, Q. et al. Effect Comparison of Both Iron Chelators on Outcomes, Iron Deposit, and Iron Transporters After Intracerebral Hemorrhage in Rats. Mol Neurobiol 53, 3576–3585 (2016). https://doi.org/10.1007/s12035-015-9302-3

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  • DOI: https://doi.org/10.1007/s12035-015-9302-3

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