Abstract
Neural stem cell secretome (NSC-S) plays an important role in neuroprotection and recovery. Studies have shown that endoplasmic reticulum stress (ER stress) is involved in the progression of traumatic brain injury (TBI) and is a crucial cause of secondary damage and neuronal death after brain injury. Whether NSC-S is engaged in ER stress and ER stress-mediated neuronal apoptosis post-TBI has not been investigated. In the study, the Feeney SD male rat model was established. The results showed that NSC-S treatment significantly improved the behavior of rats with TBI. In addition, NSC-S relieved ER stress in TBI rats and was observed by transmission electron microscopy and western blot. The specific mechanism was further elucidated that restoration was achieved by alleviating the PERK-eIF2α pathway and thus protecting neurons from apoptosis. Notably, the discovery of calumenin (CALU) in NSC-S by liquid chromatography-tandem mass spectrometry (LC–MS/MS/MS) may be related to the protective effect of NSC-S on ER stress in neurons. Also, the mechanism by which it functions may be related to ubiquitination. In summary, NSC-S improved prognosis and ER stress in TBI rats and might be a promising treatment for relieving TBI.
Graphical Abstract
Neural stem cell secretome protects neurons from apoptosis through different pathways.
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Abbreviations
- NSC-S:
-
Neural stem cell secretome
- ER Stress:
-
Endoplasmic reticulum stress
- TBI:
-
Traumatic brain injury
- ROS:
-
Reactive oxygen species
- TG:
-
Thapsigargin
- PERK:
-
RNA-dependent protein kinase
- eIF2ɑ:
-
Eukaryotic initiation factor 2ɑ
- ATF4:
-
Activating transcription factor 4
- CHOP:
-
C/EBP homologous protein
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Acknowledgements
We would like to thank Professor Weining Zhang and Associate Professor Jia Wang for their help in animal experiments.
Funding
This study was supported by the National Natural Science Foundation of China (Grant No. 81571221), the Science and Technology Cooperation Foundation of Health Biomed (Grant No. 20200605) and the Qing Lan Project of Jiangsu Province, and the National Research Foundation of Korea (2018K1A4A3A01064257, 2021R1A5A2022318).
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Y.T.L.; Conceptualization, Methodology, Data Collection, Resources, Writing-Original Draft. M.R.; Conceptualization, Data Analysis, Supervision, Writing-Original, Review, and Editing. X.R.L.; Software, Methodology. D.D.N.; Y.Z.; Y.Q.; Y.S.; T.G.; Y.Y.N.; J.W.Z.; Z.Y.W.; H.W.K.; Writing-Review and Editing. J.B.H.; Conceptualization, Methodology, Resources, Funding acquisition, Supervision, Writing-Review, and Editing. All authors read and approved the final manuscript.
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Ling, Y., Ramalingam, M., Lv, X. et al. Human neural stem cell secretome relieves endoplasmic reticulum stress-induced apoptosis and improves neuronal functions after traumatic brain injury in a rat model. J Mol Histol (2024). https://doi.org/10.1007/s10735-024-10192-7
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DOI: https://doi.org/10.1007/s10735-024-10192-7