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Electroacupuncture alleviates traumatic brain injury by inhibiting autophagy via increasing IL-10 production and blocking the AMPK/mTOR signaling pathway in rats

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Abstract

Autophagy, switched by the AMPK/mTOR signaling, has been revealed to contribute greatly to traumatic brain injury (TBI). Electroacupuncture (EA) is a promising therapeutic method for TBI, however, the underlying mechanism is still unclear. Herein, we hypothesize that the therapeutic effect of EA on TBI is associated with its inhibition on AMPK/mTOR-mediated autophagy. Sprague-Dawley rats were randomly divided into three groups: sham, TBI, and TBI + EA. TBI model was established by using an electronic controlled cortical impactor. Rats were treated with EA at 12 h after modeling, 15 min daily for 14 consecutive days. EA was applied at the acupuncture points Quchi (LI 11), Hegu (LI4), Baihui (GV20), Guanyuan (CV4), Zusanli (ST36) and Yongquan (KI1), using dense-sparse wave, at frequencies of 1 Hz, and an amplitude of 1 mA. After 3, 7 and 14 days of modeling, the modified neurological severity scale (mNSS), rota rod system, and Morris Water Maze (MWM) test showed that EA treatment promoted neurological function recovery in TBI rats. Moreover, EA treatment alleviated brain edema, pathological damage, neuronal apoptosis in TBI rats. EA improved abnormal ultrastructure, including abnormal mitochondrial morphology and increased autophagosomes, in the brain neurons of TBI rats, as measured by transmission electron microscopy, and the concentration of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP). Western blot and immunohistochemistry (IHC) assays were performed to measure the protein levels of interleukin 10 (IL-10), autophagy-related proteins and key proteins in the AMPK/mTOR signaling pathway. EA treatment increased IL-10 production, inhibited the AMPK/mTOR signaling, and inhibited excessive autophagy in TBI rats. Additionally, AMPK inhibitor Compound C treatment had similar effects to EA. Both AMPK agonist AICAR and IL-10 neutralizing antibody treatments reversed the effects of EA on the related protein levels of autophagy and the AMPK/mTOR signaling pathway, and abolished the protective effects of EA on TBI rats. In conclusion, EA treatment promoted neurological function recovery and alleviated pathological damage and neuronal apoptosis in TBI rats through inhibiting excessive autophagy via increasing IL-10 production and blocking the AMPK/mTOR signaling pathway.

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Data availability

The datasets used during the present study are available from the corresponding author upon reasonable request.

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Funding

This study was supported by the following grants:1. National Natural Science Foundation of China Youth Program (No.81904310); 2. Natural Science Basic Research Program of Shaanxi Province (No.2021JQ-729); 3. National Natural Science Foundation of China (81971049, 81671097); 4. National Natural Science Foundation of China (82074503).

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Authors and Affiliations

  1. Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Research Center of Stomatology, Xi’an Jiaotong University College of Stomatology, 98 West 5th Road, Xi’an, Shaanxi, 710004, People’s Republic of China

    Tao Wu & Dong-Yuan Cao

  2. College of Acupuncture and Tuina, Shaanxi University of Chinese Medicine, Xixian New Area, Shaanxi, 712046, People’s Republic of China

    Tao Wu & Ruihui Wang

  3. Pain Department, The Second Affiliated Hospital, Shaanxi University of Chinese Medicine, Xixian New Area, Shaanxi, 712000, People’s Republic of China

    Jiushe Kou

  4. Orthopedics Department, The Second Affiliated Hospital, Shaanxi University of Chinese Medicine, Xixian New Area, Shaanxi, 712000, People’s Republic of China

    Xuemei Li

  5. Department of Clinical Medicine, The Second Clinical Medical College, Shaanxi University of Chinese Medicine, Xixian New Area, Shaanxi Province, 712046, People’s Republic of China

    Yongchang Diwu

  6. Scientific Research Department, The Second Affiliated Hospital, Shaanxi University of Chinese Medicine, Xixian New Area, Shaanxi, 712000, People’s Republic of China

    Yuanyuan Li

Authors
  1. Tao Wu
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  2. Jiushe Kou
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  3. Xuemei Li
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  4. Yongchang Diwu
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  5. Yuanyuan Li
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  6. Dong-Yuan Cao
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  7. Ruihui Wang
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Contributions

TW performed the main experiments and write the original manuscript; J K prepared the figures and edit the manuscript; XL provide the methodology and edit the manuscript; YD and Y L performed the statistical analyses and edit the manuscript; DC designed the study, provided the most research fund and edit the manuscript; RW provided a part of research fund and edit the manuscript.

Corresponding authors

Correspondence to Dong-Yuan Cao or Ruihui Wang.

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All experimental procedures were approved by the Institutional Animal Care and Use Committee (IACUC) of Shaanxi University of Chinese Medicine.

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Wu, T., Kou, J., Li, X. et al. Electroacupuncture alleviates traumatic brain injury by inhibiting autophagy via increasing IL-10 production and blocking the AMPK/mTOR signaling pathway in rats. Metab Brain Dis 38, 921–932 (2023). https://doi.org/10.1007/s11011-022-01133-y

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