• Guang Yang, Christopher Qian, Chao Zhang, Yong Bao, Meng-Yue Liu, Fei Jiang, Wei Li, Yong Liu, Ya Ke, and Zhong-Ming Qian.
• Institute of Translational and Precision Medicine, Nantong University, Nantong, JS, China; Laboratory of Neuropharmacology of Pharmacy School, and National Clinical Research Center for Aging and Medicine of Huashan Hospital, Fudan University, Shanghai, China; Department of Geriatrics, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei, China.
• Transl Res. 2021 Mar 1; 229: 536853-68.

AbstractIron plays a key role in secondary neuronal injury after intracerebral hemorrhage (ICH), and hepcidin is able to reduce brain iron in iron-overloaded rats by down-regulating iron transport proteins including ferroportin 1 and transferrin receptor 1. These led us to hypothesize that hepcidin might reduce iron-mediated neurotoxicity by inhibiting iron accumulation in ICH brain. Here, we examined effects of Ad-hepcidin (hepcidin expression adenovirus) on the nonheme iron contents, expression of hepcidin, ferritin and iron transport proteins, neuronal cell survival, water contents in the brain and/or cerebrospinal fluid (CSF), and ICH-induced apoptosis, neurological deficit by RT-PCR, Western blot analysis, NeuN Immunofluorescence, TUNEL, Fluoro-Jade B staining, behavioral performance and Morris water-maze tests in 510 rats. We demonstrated that hepcidin could significantly suppress the ICH-induced increase in iron and ferritin in brain tissues and CSF by inhibiting expression of iron transport proteins, increase neuronal survival by attenuating ICH-induced apoptosis, reactive oxygen species, neurodegeneration and brain edema, as well as effectively improve ICH-induced behavioral and cognitive deficit in rats. The findings collectively showed that hepcidin could effectively attenuate iron-mediated secondary neuronal injury after ICH in rats. This naturally existing protein can potentially be developed into a therapeutic drug for the treatment of ICH patients.Copyright © 2020 Elsevier Inc. All rights reserved.

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