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Asiaticoside Attenuates Blood–Spinal Cord Barrier Disruption by Inhibiting Endoplasmic Reticulum Stress in Pericytes After Spinal Cord Injury

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Abstract

The blood–spinal cord barrier (BSCB) plays a vital role in the recovery of spinal cord function after spinal cord injury (SCI). Pericytes, pluripotent members of the neurovascular unit (NVU), receive signals from neighboring cells and are critical for maintaining CNS function. Therapeutic targets for the BSCB include endothelial cells (ECs) and glial cells, but few drugs target pericytes. This study was designed to explore whether asiaticoside has a positively effect on pericytes and the integrity of the BSCB. In this study, we found that asiaticoside could inhibit the loss of junction proteins just 1 day after SCI in vivo, but our in vitro study showed no significant differences in the expression of endothelial junction proteins between the control and asiaticoside treatment groups. We also found that asiaticoside could inhibit endoplasmic reticulum (ER) stress and pericyte apoptosis, which might be associated with the inhibition of junction protein reduction in ECs. Thus, we investigated the interactions between pericytes and ECs. Our results showed that asiaticoside could decrease the release of matrix metalloproteinase (MMP)-9 in pericytes and therefore upregulate the expression of junction proteins in ECs. Furthermore, the protective effect of asiaticoside on pericytes is related to the inhibition of ER stress via the MAPK signaling pathway. Taken together, our results demonstrate that asiaticoside treatment inhibits BSCB disruption and enhances functional recovery after SCI.

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Data Availability

All data supporting the findings are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank the AJE editorial team ("http://www.aje.cn") for language editing services.

Funding

This study was supported by the National Natural Science Foundation of China (grant no. 81403229).

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Author notes

  1. Zhenxin Hu, Tingting Wu, Ziheng Zhou, and Yu Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopedics, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China

    Zhenxin Hu, Nizhou Jiang & Xiliang Tian

  2. The First Clinical Medical College, Wenzhou Medical University, Wenzhou, 325035, China

    Tingting Wu, Ziheng Zhou, Qiyue Chen, Hanbing Yao, Mengchu Ji, Ge Shen, Chenling Dong, Chengge Shi & Zhixian Huang

  3. Cixi Biomedical Research Institute, Wenzhou Medical University, Ningbo, 315302, China

    Yu Zhang

  4. Department of Ultrasonography, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China

    Nan Han

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  1. Zhenxin Hu
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Contributions

Zhenxin Hu, Tingting Wu, and Xiliang Tian designed the study. Ziheng Zhou, Qiyue Chen, Hanbing Yao, Mengchu Ji, and Ge Shen prepared materials, implemented the molecular biology experiment, and collected data. Chengge Shi, Chenling Dong, Zhixian Huang, and Nizhou Jian processed the data. Zhenxin Hu, Tingting Wu, and Ziheng Zhou composed the draft manuscript. Yu Zhang and Zhenxin Hu implemented the molecular biology experiment, processed the data, and revised the manuscript. Nan Han and Xiliang Tian revised the manuscript. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Nan Han or Xiliang Tian.

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Hu, Z., Wu, T., Zhou, Z. et al. Asiaticoside Attenuates Blood–Spinal Cord Barrier Disruption by Inhibiting Endoplasmic Reticulum Stress in Pericytes After Spinal Cord Injury. Mol Neurobiol 61, 678–692 (2024). https://doi.org/10.1007/s12035-023-03605-3

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