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

Yang Cao 1 • Yin Li 1 • Chao He 1 • Feng Yan 1 • Jian-Ru Li 1 • Hang-Zhe Xu 1 • Jian-Feng Zhuang 1 • Hang Zhou 1 • Yu-Cong Peng 1 • Xiong-Jie Fu 1 • Xiao-Yang Lu 1 • Yuan Yao 1 • Yu-Yu Wei 1 • Yun Tong 1 • Yi-Fu Zhou   • Lin Wang 1

1 Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China




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.



Subarachnoid hemorrhage; Ferroptosis; Inflammation ; Liproxstatin-1