Selective Ferroptosis Inhibitor Liproxstatin-1 Attenuates Neurological Deficits and Neuroinflammation After Subarachnoid Hemorrhage

• 作者: Yang Cao Yin Li Chao He Feng Yan Jian-Ru Li Hang-Zhe Xu Jian-Feng Zhuang Hang Zhou Yu-Cong Peng Xiong-Jie Fu Xiao-Yang Lu Yuan Yao Yu-Yu Wei Yun Tong Yi-Fu Zhou Lin Wang
• 来源期刊: 神经科学通报（英文版）
• 年，卷（期）: 2021,（4）
• 所属期刊栏目: Original Articles
• 页码范围: 535-549
• 页数: 15页
• 语种: 英文

摘要

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 acylCoA 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.