Hepcidin/HIF-1α is involved in the endogenous recovery and ferroptosis after cerebral ischemia in mice.

Abstract

It is common to witness a spontaneous endogenous recovery process with the potential mechanisms involving the remyelination, nerve regeneration, and synaptic plasticity, which might be vital for the neurological rehabilitation after cerebral ischemic stroke. Iron homeostasis is considered to be crucial for myelination and neuronal metabolic processes, and Hepcidin is an important factor in regulating iron homeostasis and ferroptosis. Hypoxia-inducible factor (HIF) is an important hypoxia tolerance factor and can regulate cell survival in hypoxia environment, which is critical to regulate iron homeostasis as well. Nevertheless, the effect of Hepcidin on endogenous injury repair during cerebral ischemia recovery period and whether Hepcidin could regulate ferroptosis via HIF-1α remain unclear. Here, we established the distal middle cerebral artery occlusion (dMCAO) mice model to investigate the effect of Hepcidin on endogenous injury repair and ferroptosis during cerebral ischemia recovery and HIF-1α-associated mechanisms. Our results indicated that Hepcidin/HIF-1α pathway played a crucial role in regulating ferroptosis as well as endogenous injury repair and subsequent neurological recovery after cerebral ischemia, serving as a possible target for the treatment of recovery after stroke.