Journal Article

Inhibition of Ferroptosis Alleviates Early Brain Injury After Subarachnoid Hemorrhage In Vitro and In Vivo via Reduction of Lipid Peroxidation

Liu, Yao, Wu, Pei, Li, Yuchen, Liu, Binbing, Bihl, Ji, Shi, Huaizhang, Tian, Yang, Wang, Jinju

2021

Overview

Subarachnoid hemorrhage (SAH) is a serious cerebrovascular disease with high mortality, and the mean age at morbidity is younger than in other types of stroke. Early brain injury (EBI) plays a key role in the poor prognoses of SAH. In EBI, multiple forms of cell death have been identified and well studied; however, the role of ferroptosis has not been elucidated. Hence, in this study, we developed an in vivo (SAH rat model) and in vitro model (SH-SY5Y oxyhemoglobin injury model) to understand the role of ferroptosis in EBI, then explored the protective mechanism of ferrostatin-1 (Fer-1). Firstly, we found that neurological scores, blood–brain barrier permeability, brain edema deteriorated after SAH in the in vivo model, cell viability was decreased after SAH in both cortex and SH-SY5Y cells. Further, iron content in cortex was increased after SAH, while transferrin receptor 1 and ferroportin (Fpn) were increased in oxyhemoglobin-treated in vitro model. Additionally, glutathione content and glutathione peroxidase 4 activity were reduced in SAH rats, and lipid peroxides were increased in the oxyhemoglobin-treated cells. Finally, administration of Fer-1 upregulated Fpn and decreased the iron content, then improved the lipid peroxidation and EBI. However, Fer-1 had no effect on the apoptosis. Our study indicated that the ferroptosis was involved in EBI of SAH, and the inhibitor Fer-1 provided neuroprotection against EBI by alleviating ferroptosis, the potential protective mechanism might be via suppressing lipid peroxidation.

• Publisher: Springer US,Springer Nature B.V
• Subject: Animals / Apoptosis / Biomedical and Life Sciences / Biomedicine / Blood clots / Blood-brain barrier / Blood-Brain Barrier - pathology / Brain Edema - etiology / Brain Edema - pathology / Brain Injuries - etiology / Brain injury / Carotid arteries / Cell Biology / Cell Death / Cell Line, Tumor / Cell Survival / Cell viability / Cerebrovascular diseases / Clinical trials / Edema / Ferroptosis / Glutathione / Glutathione peroxidase / Hemorrhage / Humans / Iron / Iron - metabolism / Lipid Peroxidation / Lipids / Male / Medical research / Membrane permeability / Mitochondria - metabolism / Mitochondria - ultrastructure / Morbidity / Neurobiology / Neurons - pathology / Neuroprotection / Neurosciences / Original Research / Permeability / Rats / Rats, Sprague-Dawley / Subarachnoid hemorrhage / Subarachnoid Hemorrhage - complications / Survival Analysis / Transferrins / Traumatic brain injury / Veins & arteries