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Selective Ferroptosis Inhibitor Liproxstatin-1 Attenuates Neurological Deficits and Neuroinflammation After Subarachnoid Hemorrhage / 神经科学通报·英文版
Neuroscience Bulletin ; (6): 535-549, 2021.
Article de Zh | WPRIM | ID: wpr-951999
Bibliothèque responsable: WPRO
ABSTRACT
Ferroptosis is a form of iron-dependent regulated cell death. Evidence of its existence and the effects of its inhibitors on subarachnoid hemorrhage (SAH) is still lacking. In the present study, we found that liproxstatin-1 protected HT22 cells against hemin-induced injury by protecting mitochondrial functions and ameliorating lipid peroxidation. In in vivo experiments, we demonstrated the presence of characteristic shrunken mitochondria in ipsilateral cortical neurons after SAH. Moreover, liproxstatin-1 attenuated the neurological deficits and brain edema, reduced neuronal cell death, and restored the redox equilibrium after SAH. The inhibition of ferroptosis by liproxstatin-1 was associated with the preservation of glutathione peroxidase 4 and the downregulation of acyl-CoA synthetase long-chain family member 4 as well as cyclooxygenase 2. In addition, liproxstatin-1 decreased the activation of microglia and the release of IL-6, IL-1β, and TNF-α. These data enhance our understanding of cell death after SAH and shed light on future preclinical studies.
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Texte intégral: 1 Indice: WPRIM langue: Zh Texte intégral: Neuroscience Bulletin Année: 2021 Type: Article
Texte intégral: 1 Indice: WPRIM langue: Zh Texte intégral: Neuroscience Bulletin Année: 2021 Type: Article