Xiao-Feng Qu1,2, Tian-Yu Liang1, De-Gang Wu1,3, Nian-Sheng Lai1,3, Ru-Ming Deng1,4, Chao Ma1, Xiang Li1, Hai-Ying Li1, Yi-Zhi Liu1, Hai-Tao Shen1, Gang Chen1. 1. Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China. 2. Department of Neurology, The First People's Hospital of Yancheng, Yancheng, Jiangsu Province, China. 3. Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui Province, China. 4. Department of Neurosurgery, The People's Hospital of Bozhou, Bozhou, Anhui Province, China.
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.
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.
Authors: Andreas Linkermann; Rachid Skouta; Nina Himmerkus; Shrikant R Mulay; Christin Dewitz; Federica De Zen; Agnes Prokai; Gabriele Zuchtriegel; Fritz Krombach; Patrick-Simon Welz; Ricardo Weinlich; Tom Vanden Berghe; Peter Vandenabeele; Manolis Pasparakis; Markus Bleich; Joel M Weinberg; Christoph A Reichel; Jan Hinrich Bräsen; Ulrich Kunzendorf; Hans-Joachim Anders; Brent R Stockwell; Douglas R Green; Stefan Krautwald Journal: Proc Natl Acad Sci U S A Date: 2014-11-10 Impact factor: 11.205