Hemolytic Iron Regulation in Traumatic Brain Injury and Alcohol Use

Abstract

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) which 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 a rat model of TBI by altering the iron management pathways. We found large accumulations of free iron at the site of hemorrhage with evidence of hemolytic activity. Our observations demonstrate that alcohol use can alter the three distinct iron management pathways: transferrin/hemosiderin binding, lipocalin 2/heme oxygenase 1/ferritin system, and possible microglial phagocytosis. Presence of alcohol prolonged the expression of lipocalin 2 as well as increased and sustained levels of ferritin, while the combined effects of alcohol and TBI elevated the levels of heme oxygenase 1 faster than TBI alone. The hippocampus, neocortex, ventricles, and around vessels near the site of impact appeared to be the prominent brain regions of induction. In addition, we provide evidence that microglia my also play a role in iron management through RBC phagocytosis.

Dichrocephala integrifolia Aqueous Extract Antagonises Chronic and Binges Ethanol Feeding-Induced Memory Dysfunctions: Insights into Antioxidant and Anti-Inflammatory Mechanisms

“…e present study was designed with the purpose, to assess the effects of an aqueous extract from the leaves of D. integrifolia on a mouse model of chronic ethanol feeding plus ethanol binges-induced oxidative stress, neuroinflammation, and memory dysfunctions in Swiss mice. e Lieber-DeCarli ethanol diet, which is a valid model to induce ethanol-use disorders [49] was used. Chronic ethanol exposures are among the leading causes of learning and memory disabilities, spatial working memory impairment as well as cognitive deficits [50,51].…”