| Popis: |
Hemorrhage is often a major component of traumatic brain injury (TBI). Red blood cells (RBCs) accumulated at the hemorrhagic site undergo hemolysis upon energy depletion. Hemolysis of RBCs is expected to release free iron into the central nervous system (CNS) that must be managed to prevent iron neurotoxicity. Here, we examine the hypothesis that chronic alcohol consumption, as a secondary stressor, may increase iron toxicity in an animal model of TBI by altering the iron management pathways. To our best knowledge, this innovative idea with significant scientific premises has not been examined to date. We found huge accumulation of free irons at the site of hemorrhage with evidence of hemolytic activity. Our observation showed that alcohol use altered the three distinct iron management pathways of transferrin/hemosiderin binding, lipocalin 2/heme oxygenase 1/ferritin system, and microglial phagocytosis. Presence of alcohol prolonged the expression of lipocalin 2 at the site of hemorrhage compared with injury alone, while the combined effects of alcohol and TBI elevated the levels of heme oxygenase 1 earlier than TBI alone. Hippocampus, neocortex, and around vessels near the site of impact appeared to be the prominent brain regions of induction. The presence of alcohol notably increased the levels of ferritin that sustained for up to 7 days. We also provide evidence that microglia also play a role in iron management through RBC phagocytosis. These results reveal the intricacy and plasticity of iron management and highlight the importance of proper iron regulation in the CNS. |
