Glutathione peroxidase 4 participates in secondary brain injury through mediating ferroptosis in a rat model of intracerebral hemorrhage.

This study was designed to investigate the changes in protein levels, as well as potential role and mechanism of GPX4 in SBI following ICH using a Sprague-Dawley (SD) rat model of ICH induced by autologous blood injection into the right basal ganglia. Firstly, GPX4 protein levels in the brain were reduced gradually and bottomed out at 24 h after ICH, compared with the Sham group. Secondly, genetic-overexpression of GPX4 effectively increased level of GPX4 in the brain, and clearly relieved neuronal dysfunction, brain edema, blood brain barrier (BBB) injury, oxidative stress and inflammation after ICH. In contrast, inhibiting GPX4 with a specific pharmacological inhibitor or genetic knockdown exacerbated SBI after ICH. Finally, Ferrostatin-1, a chemical inhibitor of ferroptosis, was used to explore the role of ferroptosis in brain injury after ICH. The results suggest that inhibiting ferroptosis can significantly alleviate SBI after ICH. In summary, our work indicated that GPX4 contributes to SBI following ICH by mediating ferroptosis. Therefore, inhibiting ferroptosis with specific inhibitors or upregulation of GPX4 may be a potential strategy to ameliorate brain injury induced by ICH. PMID: 30205109 [PubMed - as supplied by publisher]
Source: Brain Research - Category: Neurology Authors: Tags: Brain Res Source Type: research