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Acupuncture Ameliorates Neuronal Cell Death, Inflammation, and Ferroptosis and Downregulated miR-23a-3p After Intracerebral Hemorrhage in Rats

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Abstract

Baihui-penetrating-Qubin acupuncture is frequently used to treat intracerebral hemorrhage (ICH) in China. Acupuncture affects multiple microRNAs in diseases. MicroRNA-23a-3p (miR-23a-3p) has been demonstrated to be up-regulated in ICH patients. Herein, the effect of Baihui-penetrating-Qubin acupuncture on miR-23a-3p expression after ICH and the role of miR-23a-3p in ICH were discussed. A rat model of ICH was induced by infusing autologous blood into caudate nucleus. Acupuncture was performed after ICH once a day for 30 min. After 3 consecutive days of acupuncture, the neurobehavioral function, brain edema, neuronal cell death, inflammation, ferroptosis, nuclear factor E2-like 2 (NFE2L2) signaling and miR-23a-3p levels in brain tissues were analyzed. Additionally, antagomiR-23a-3p was injected into rats 3 days prior to ICH modeling to analyze the function of miR-23a-3p in neuronal cell death, inflammation, ferroptosis, and NFE2L2 signaling. Acupuncture relieved the ICH-induced neurological function deficits, increases in brain water content and Fluoro-Jade B (FJB)-positive cells and release of proinflammatory cytokines. Acupuncture also alleviated ferroptosis and decreased miR-23a-3p expression, as evidenced by the increased NFE2L2 nuclear translocation and expressions of heme oxygenase-1 and glutathione peroxidase 4 and the decreased iron and malondialdehyde contents and reactive oxygen species accumulation. Additionally, antagomiR-23a-3p inhibited the ICH-induced increases in FJB-positive cells, release of proinflammatory cytokines, ferroptosis, and promoted NFE2L2 activation. Notably, the binding site of miR-23a-3p existed in NFE2L2. Taken together, acupuncture may alleviate the neuronal cell death, inflammation, and ferroptosis after ICH by down-regulating miR-23a-3p. This study provides a potential mechanism underlying the Baihui-penetrating-Qubin acupuncture improving the early injury after ICH.

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Data Availability

The data in this study are available from the corresponding author on reasonable request.

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GraphPad Prism 8 software was employed to carry out statistical analyses.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (No. 81904305), the Heilongjiang University of Chinese Medicine Doctoral Innovation Foundation (No. 2017bs05), the Heilongjiang Provincial Postdoctoral Science Foundation (No. LBH-Z12249), the Project of Science and Technology of Education Department of Heilongjiang Province (No. 12531633) and the Foundation of Heilongjiang University of Chinese Medicine (No. 2019PT10).

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Wei Zou designed the study. Material preparation, data collection, and analysis were performed by Ying Kong, Shulin Li, Miao Zhang, Wenting Xu, Qiuxin Chen, Lihong Zheng, and Peng Liu. The first draft of the manuscript was written by Ying Kong. All authors read and approved the final manuscript.

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Correspondence to Wei Zou.

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The authors have no potential conflicts of interest to disclose.

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Animal experiments were performed and approved by the ethics committee of Second Affiliated Hospital of Heilongjiang University of Chinese Medicine.

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Kong, Y., Li, S., Zhang, M. et al. Acupuncture Ameliorates Neuronal Cell Death, Inflammation, and Ferroptosis and Downregulated miR-23a-3p After Intracerebral Hemorrhage in Rats. J Mol Neurosci 71, 1863–1875 (2021). https://doi.org/10.1007/s12031-020-01770-x

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  • DOI: https://doi.org/10.1007/s12031-020-01770-x

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