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Tetrandrine Ameliorates Traumatic Brain Injury by Regulating Autophagy to Reduce Ferroptosis

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Abstract

Traumatic brain injury (TBI) is the leading cause of death and disability in trauma patients. However, the effects and mechanism of autophagy after TBI remain unclear. This study aimed to investigate whether tetrandrine could ameliorate TBI through autophagy to reduce ferroptosis. A mice model for TBI was implemented. Behavioral and histomorphological experiments were performed to evaluate outcomes of the mice. The ferroptosis levels was detected by Perls staining. Enzyme-linked immunosorbent assay (ELISA) was applied to detect malondialdehyde (MDA), glutathione (GSH), and glutathione peroxidase 4 (GPX4) levels in the brain tissue. Western blot test was performed to detect Beclin 1, light chain 3 (LC3) II/I, p62, GPX4, SCL7A11, and ferritin heavy chain 1 (FTH1) levels, and the expression of LC3B, Beclin 1, GPX4, and FTH1 in the brain tissue was detected by immunofluorescence (IF). The behavioral and histomorphological results demonstrated that tetrandrine improved the neurological function and cerebral edema on days 1, 3, and 7 after TBI. The ELISA results suggested that tetrandrine reduced the MDA concentration and increased GSH concentration on days 1, 3, and 7 after TBI. IF staining and Perls staining reflected that tetrandrine promoted autophagy and inhibited ferroptosis on days 1, 3, and 7 after TBI, respectively. Tetrandrine further improved the neurological function, cerebral edema, autophagy, and ferroptosis on days 1, 3, and 7 after TBI after adding the autophagy inducer rapamycin. The effect of TET in alleviating TBI increased with the increase of time and dose. Tetrandrine ameliorated TBI by regulating autophagy to reduce ferroptosis, providing a new therapeutic strategy for TBI.

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Acknowledgements

The authors would like to thank the Laboratory Animal of University of South China for their technical assistance.

Funding

This work was supported by the Hunan Provincial Natural Science Fund (No. 2019JJ80056); Natural Science Foundation of Hunan Province (No. 2021JJ70045); and General Project of Hunan Provincial Department of Education (No. 20C1587).

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Author notes

  1. Huan Liu and Shiqing He contributed to this work equally. They are cofirst authors.

Authors and Affiliations

  1. Department of Cardiology, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China

    Huan Liu

  2. Department of Neurosurgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China

    Shiqing He, Jianpeng Wang, Chong Li, Yongshi Liao, Qin Zou & Rui Chen

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  1. Huan Liu
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  2. Shiqing He
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Contributions

Conceptualization: HL, SH, QZ, and RC; Data curation: SH, JW, and YL; Methodology: HL, SH, JW, CL, and YL; Formal analysis and investigation: QZ, HL, SH, JW, CL, and YL; Writing—original draft preparation: HL and SH; Writing—review and editing: QZ and RC; Funding acquisition: QZ and RC; Resources: QZ and RC; and Supervision: RC.

Corresponding authors

Correspondence to Qin Zou or Rui Chen.

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The authors declare that they have no conflicts of interest.

Ethical Approval

This study was approved by the Animal Experiment Ethics Committee of University of South China and conducted in strict accordance with the National Institutes of Health Guidelines for the Care and Use of Experimental Animals.

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Supplementary Information

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11064_2022_3553_MOESM1_ESM.jpg

Supplementary Figure 1. Histomorphological damage on day 1 and day 3 after TBI. Scale bar = 100 µm; The magnifications were 40x, 100x, and 400x (JPG 4639 kb)

11064_2022_3553_MOESM2_ESM.jpg

Supplementary Figure 2. IF was applied to detect the expression of LC3B on day 1 and day 3 after TBI. Scale bar = 100 µm; The magnification was 400x. (LC3, light chain 3) (JPG 3019 kb)

11064_2022_3553_MOESM3_ESM.jpg

Supplementary Figure 3. Beclin 1, GPX4, and FTH1 expression on day 1 and day 3 after TBI was measured by IF. Scale bar = 100 µm; The magnification was 400x. (GPX4, glutathione peroxidase 4. FTH1, ferritin heavy chain 1) (JPG 8423 kb)

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Liu, H., He, S., Wang, J. et al. Tetrandrine Ameliorates Traumatic Brain Injury by Regulating Autophagy to Reduce Ferroptosis. Neurochem Res 47, 1574–1587 (2022). https://doi.org/10.1007/s11064-022-03553-9

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  • DOI: https://doi.org/10.1007/s11064-022-03553-9

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