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

Autor: Jinju Wang, Yao Liu, Huaizhang Shi, Pei Wu, Ji C. Bihl, Binbing Liu, Yang Tian, Yuchen Li
Rok vydání: 2020
Předmět:
Zdroj: Cellular and Molecular Neurobiology. 41:263-278
ISSN: 1573-6830
0272-4340
DOI: 10.1007/s10571-020-00850-1
Popis: 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.
Databáze: OpenAIRE
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