Abstract
Cerebral ischemia represents a major cause of disability, yet its precise mechanism remains unknown. In addition, ischemia-reperfusion injury which occurs during the blood recovery process increases the risk of mortality, and is not adequately addressed with current treatment. To improve therapeutic options, it is important to explore the vital substances that play a pivotal role in ischemia-reperfusion injury. This study is the first to investigate the role of IL-32, a vital pro-inflammatory factor, in models of cerebral ischemia-reperfusion injury. The results showed that IL-32 was highly expressed in both in vivo and in vitro models. The proteins of the NOD/MAPK/NF-κB pathway were also up-regulated, indicating a potential signaling pathway mechanism. Inhibition of IL-32 and blocking of the NOD/MAPK/NF-κB pathway increased cell survival, decreased the level of inflammatory factors and inflammasomes, and attenuated nitrosative stress. Taken together, the results show that inhibition of IL-32 expression ameliorates cerebral ischemia-reperfusion injury via the NOD/MAPK/NF-κB signaling pathway. The findings in this study reveal that IL-32 is a vital target of ischemia-reperfusion injury, providing a new avenue for treatment development.
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All authors contributed to the study conception and design. The design and writing of the manuscript were performed by Chao Liu. Data collection and analysis were performed by Chao Liu, Xiaohui Xu and Chao Huang. All functional experiments were conducted by Dandan Shang and Li Zhang.
The second draft of the manuscript was written by Yupeng Wang. All authors read and approved the final manuscript.
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All procedures involving animal experiments were approved by the Animal Research Ethics Committee of Luoyang Central Hospital Affiliated to Zhengzhou University, Henan, China, and conducted according to the Animal Protection Law of the People’s Republic of China-2009.
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Liu, C., Xu, X., Huang, C. et al. Inhibition of IL-32 Expression Ameliorates Cerebral Ischemia-Reperfusion Injury via the NOD/MAPK/NF-κB Signaling Pathway. J Mol Neurosci 70, 1713–1727 (2020). https://doi.org/10.1007/s12031-020-01557-0
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DOI: https://doi.org/10.1007/s12031-020-01557-0