Abstract WMP75: Functional Role of Hemojuvelin in Acute Ischemic Stroke

Abstract

Background and Purpose: Hemojuvelin (HJV)-hepcidin axis has been shown an important pathophysiological mechanism in acute liver and kidney injuries, but little is known about the role of HJV in acute stroke. Our aim was to establish the temporal expression and function of HJV during acute ischemic stroke (AIS). Methods: C57BL/6J mice receiving 1-hour middle cerebral artery occlusion (MCAO) and primary cortical neurons subjected to oxygen and glucose deprivation (OGD) were performed to determine the expression profile of HJV after AIS. Infarct sizes and behavior scores at 72 hours post MCAO on HJV knockout (129S-Hfe2tm1Nca/J) and wild type (129S) mice were compared to determine the role of HJV. In addition, patients with AIS were recruited and plasma samples were collected for the measurement of HJV. Results: The expression of HJV protein in mice brain was noted early at 3 hours after MCAO and increased significantly at 72 hours after MCAO, along with the appearance of its downstream protein- hepcidin at the same time point. In cultured cortical neurons, the expression of HJV protein also increased remarkably at 24-48 hours after 3 hours OGD stimulation. Importantly, HJV knockout mice had significantly less infarct size and expression of cleaved caspase-3 protein compared with wild type mice at 72 hours post MCAO. In human subjects, HJV expression can be seen in autopsy brain tissues from stroke patients with mortality outcome. In addition, among 112 AIS patients, plasma level of HJV within 48 hours after stroke was an independent poor prognostic predictor of functional outcome at 3 months post-stroke (odds ratio: 1.780; 95% confidence intervals: 1.032-3.073; p =0.038). Conclusions: HJV- hepcidin axis is existing in mice brain and participating in the mechanisms of post stroke neuronal injury. Clinically, plasma HJV may be a potential outcome indicator in patients with AIS.