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Possible Role of Raf-1 Kinase in the Development of Cerebral Vasospasm and Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats

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A Correction to this article was published on 16 April 2024

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Abstract

This study aims to clarify the potential role of Raf-1 kinase in cerebral vasospasm (CVS) and early brain injury (EBI) after subarachnoid hemorrhage (SAH). Two experimental SAH models in rats, including cisterna magna double injection model for CVS study and prechiasmatic cistern single injection model for EBI study, were performed in this research. As a specific inhibitor of Raf-1, BAY 43-9006 was used in this study. In CVS study, time course study showed that the basilar artery exhibited vasospasm after SAH and became most severe at day 5, and the phosphorylation of Raf-1 had the same trends, while both vasospasm and the phosphorylation of Raf-1 induced by SAH were inhibited by BAY 43-9006 treatment. In addition, BAY 43-9006 treatment significantly reversed the phosphorylation of ERK1/2 and the activation of NF-κB induced by SAH and decreased the messenger RNA (mRNA) levels of IL-6 and IL-1β. In EBI study, BAY 43-9006 treatment significantly suppressed the brain injury induced by SAH. Besides, BAY 43-9006 inhibited the phosphorylation of Raf-1 and ERK1/2; decreased the protein levels of COX-2, VEGF, and MMP-9; and reversed the activation of NF-κB induced by SAH. These results demonstrate that Raf-1 kinase contributes to CVS and EBI after SAH by enhancing the activation of the Raf-1/ERK1/2 and Raf-1/NF-κB signaling pathways, and that the inhibition of these pathways might offer new treatment strategies for CVS and EBI.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (Nos. 81371279, 81422013, and 81471196), Jiangsu Province’s Outstanding Medical Academic Leader program (No. LJ201139), Scientific Department of Jiangsu Province (No. BL2014045) and Suzhou Government (Nos. LCZX201301, SZS201413, and SYS201332), and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurosurgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu Province, People’s Republic of China

    Jian Zhang, Xiang Xu, Dai Zhou, Haiying Li, Wanchun You, Zhong Wang & Gang Chen

  2. Institute of Neuroscience, Soochow University, Suzhou, Jiangsu Province, China

    Gang Chen

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  1. Jian Zhang
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  7. Gang Chen
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Correspondence to Zhong Wang or Gang Chen.

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Jian Zhang and Xiang Xu contributed equally to this work.

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Zhang, J., Xu, X., Zhou, D. et al. Possible Role of Raf-1 Kinase in the Development of Cerebral Vasospasm and Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats. Mol Neurobiol 52, 1527–1539 (2015). https://doi.org/10.1007/s12035-014-8939-7

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