Hemolytic iron regulation in traumatic brain injury and alcohol use

Hemorrhage is a major component of traumatic brain injury (TBI). Red blood cells, accumulated at the hemorrhagic site, undergo hemolysis upon energy depletion and release free iron into the central ner-vous system. This iron must be managed to prevent iron neurotoxicity and ferroptosis. As prior alcohol consumption is often associated with TBI, we examined iron regulation in a rat model of chronic alcohol feeding subjected to fluid percussion-induced TBI. We found that alcohol consumption prior to TBI altered the expression profiles of the lipocalin 2/heme oxygenase 1/ferritin iron management system. Notably, unlike TBI alone, TBI following chronic alcohol consumption sustained the expression of all three regulatory proteins for 1, 3, and 7 days post-injury. In addition, alcohol significantly affected TBI-induced expression of ferritin light chain at 3 days post-injury. We also found that alcohol exacerbated TBI-induced activation of microglia at 7 days post-injury. Finally, we propose that microglia may also play a role in iron management through red blood cell clearance.(c) 2023 Elsevier Inc. All rights reserved.

Automated summary

Hemorrhage is a significant aspect of traumatic brain injury (TBI), and alcohol consumption prior to TBI can alter iron regulation, exacerbate TBI-induced microglia activation, and sustain the expression of regulatory proteins for several days post-injury. Additionally, microglia may play a role in iron management through red blood cell clearance. This study provides valuable insights into the relationship between alcohol and TBI, as well as the importance of iron management in brain injury recovery.