Selective Ferroptosis Inhibitor Liproxstatin-1 Attenuates Neurological Deficits and Neuroinflammation After Subarachnoid Hemorrhage
- Author:
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
1
;
Lin WANG
1
Author Information
- Publication Type:Journal Article
- Keywords: Ferroptosis; Inflammation; Liproxstatin-1; Subarachnoid hemorrhage
- From: Neuroscience Bulletin 2021;37(4):535-549
- CountryChina
- Language:Chinese
- 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.
