CNS Neurosci Ther. 2021 Apr;27(4):449-463.doi: 10.1111/cns.13548. Epub 2020 Dec 12.

Acyl-CoA synthetase long chain family member 4 plays detrimental role in early brain injury after subarachnoid hemorrhage in rats by inducing ferroptosis

Xiao-Feng Qu  1   2 Tian-Yu Liang  1 De-Gang Wu  1   3 Nian-Sheng Lai  1   3 Ru-Ming Deng  1   4 Chao Ma  1 Xiang Li  1 Hai-Ying Li  1 Yi-Zhi Liu  1 Hai-Tao Shen  1 Gang Chen  1 Affiliations

Free PMC article

Abstract

Aims: Acyl-CoA synthetase long chain family member 4 (ACSL4) is closely related to tumor genesis and development in certain tissues. However, the function of ACSL4 in early brain injury (EBI) caused by subarachnoid hemorrhage (SAH) is unclear. In this study, we investigated the expression patterns and role of ACSL4 in SAH and post-SAH EBI using a rat model of SAH.

Methods: The rat model of SAH was induced by autologous blood injection into the prechiasmatic cistern of rats. We also used two specific inhibitors of ferroptosis (Ferrostatin-1 and Liproxstatin-1) to investigate the role of ferroptosis in EBI.

Results: We found that ACSL4 levels in brain tissue increased significantly in post-SAH EBI. Inhibiting the expression of ACSL4 using small interfering RNAs alleviated inflammation, blood-brain barrier (BBB) impairment, oxidative stress, brain edema, and behavioral and cognitive deficits, and increased the number of surviving neurons, after SAH. Similar effects were obtained by suppressing ferroptosis.

Conclusions: ACSL4 exacerbated SAH-induced EBI by mediating ferroptosis. These findings may provide a theoretical basis for potential therapy aimed at alleviating post-SAH EBI.

Keywords: acyl-CoA synthetase long chain family member 4; early brain injury; ferroptosis; subarachnoid hemorrhage.

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