Role Of Hepcidin And Its Downstream Proteins In Early Brain Injury After Experimental Subarachnoid Hemorrhage In Rates

Early brain injury (EBI) is considered as a new mechanism of subarachnoid hemorrhage (SAH). The present work aimed to study the pathophysiology of EBI and explore potential therapeutic options of Hepcidin and its downstream proteins. One hundred and thirty-two male Sprague-Dawley rats were randomly assigned to the following groups (24 in each):sham, SAH, SAH+ Hepcidin, SAH+ Hepcidin-targeting small interfering ribonucleic acid (siRNA), and SAH+ scramble siRNA. Three Hepcidin-targeting siRNAs and one scramble siRNA for Hepcidin were injected 24 h before hemorrhage induction, and Hepcidin protein was injected 30 min before it. Rats were neurologically evaluated at 24 h and euthanized at 72 h. Protein expression of Hepcidin, ferroportin-1 (FPN-1), and ceruloplasmin (CP) was measured by immunohistochemistry and Western blotting. Other outcome measures included brain water content and blood-brain barrier (BBB) leakage. The expression of Hepcidin increased in the cerebral cortex and hippocampus after experimental SAH compared with the sham group, and Hepcidin also lowered the expression of its downstream proteins, FPN-1 and CP. SAH group had lower neurological scores and high brain water content and BBB permeability (P＜0.05). Down-regulation of FPN-1 and CP caused by Hepcidin enhanced iron-dependent oxidative damage and it might be the potential mechanism of SAH.