Hepcidin Attenuates the Secondary Neuronal Injury after Intracerebral Hemorrhage in Rats

Abstract

Iron 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. These led us to hypothesize that hepcidin might reduce iron-mediated neurotoxicity by inhibiting iron accumulation in ICH brain. Here, we tested our hypothesis in 510 rats and demonstrated for the first time that hepcidin could significantly suppress the ICH-induced increase in iron and ferritin in brain tissues and cerebrospinal fluid by inhibiting expression of iron transport proteins, increase neuronal survival by attenuating ICH-induced apoptosis, neurodegeneration and brain edema, as well as effectively improve ICH-induced behavioral and cognitive deficit in rats. We concluded that hepcidin could effectively attenuate iron-mediated secondary neuronal injury after ICH in rats. This naturally existing protein which is biodegradable, nontoxic, and non-immunogenic can potentially be developed into a therapeutic drug for the treatment of ICH patients. Funding: The studies were supported by the National Natural Science Foundation of China (NSFC31330035-ZMQ, NSFC31571195-ZMQ), the Competitive Earmarked Grants of The Hong Kong Research Grants Council (GRF14111815-KY, GRF 14167817-KY, GRF14107616-KY), Hong Kong Health & Medical Research Fund (HMRF: 03141436-KY), Hong Kong Innovation and Technology Fund (ITS/163/16-KY), and the National 973 Programs (2014CB541604-ZMQ). Conflict of interest: The authors declare that they have no conflict of interest. Ethical Approval Statement: The Health Department of Hong Kong and Shanghai Government and the Animal Research Ethics Committee of The Chinese University of Hong Kong and Fudan University approved the experimental procedures of this study and the care and handling of the animals were in accord with National Institutes of Health guidelines.