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A combination of umbilical cord mesenchymal stem cells and monosialotetrahexosy 1 ganglioside alleviates neuroinflammation in traumatic brain injury

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Abstract

Neuro-inflammation and activated microglia play important roles in neuron damage in the traumatic brain injury (TBI). In this study, we determined the effect of neural network reconstruction after human umbilical cord mesenchymal stem cells (UMSCs) combined with monosialotetrahexosy 1 ganglioside (GM1) transplantation and the effect on the neuro-inflammation and polarization of microglia in a rat model of TBI, which was established in male rats using a fluid percussion brain injury device. Rats survived until day 7 after TBI were randomly treated with normal control (NC), saline (NS), GM1, UMSCs, and GM1 plus UMSCs. Modified neurological severity score (mNSS) was assessed on days 7 and 14, and the brain tissue of the injured region was collected. Immunofluorescence, RT-PCR, and western blot analysis found that inhibitory neuro-inflammatory cytokines TGF-β and CD163 protein expression levels in injured brain tissues were significantly increased in rats treated with GM1 + UMSCs, GM1, or UMSCs and were up-regulated compared to saline-treated rats. Neuro-inflammatory cytokines IL-6, COX-2 and iNOS protein expressions were down-regulated compared to rats treated with saline. The protein expression levels of NE, NF-200, MAP-2 and β-tubulin III were increased in the injured brain tissues from rats treated with GM1 + UMSCs, or GM1 and UMSCs alone compared to those in the rats treated with NS. The protein expression levels in rats treated with GM1 plus UMSCs were most significant on day 7 following UMSC transplantation. The rats treated with GM1 plus UMSCs had the lowest mNSS compared with that in the other groups. These data suggest that UMSCs and GM1 promote neural network reconstruction and reduce the neuro-inflammation and neurodegeneration through coordinating injury local immune inflammatory microenvironment to promote the recovery of neurological functions in the TBI.

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Availability of data and materials

The datasets used and/or analyzed during the present study are available from the corresponding author on a reasonable request. YF, WQ, SK, and ZZ confirm the authenticity of all the raw data during this study.

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (grant no. 81870984), the National Key R&D Program Intergovernmental Cooperation on International Scientific and Technological Innovation of the Ministry of Science and Technology of China (grant no. 2017YFE0110400), the Hebei Natural Science Foundation General Project–Beijing-Tianjin-Hebei Basic Research Cooperation Project (grant no. H2018206675), the Special Project for the Construction of Hebei Province International Science and Technology Cooperation Base (grant no. 193977143D), the Projects on Training of outstanding Clinical Medical Personnel and Basic Research Projects of Hebei Province in 2017 and 2019.

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Authors and Affiliations

  1. Department of Neurosurgery, The Second Hospital of Hebei Medical University, 215 Heping West Road, Shijiazhuang, 050000, Hebei, People’s Republic of China

    Yanwei Fang, Xin Li, Qianxu Jin, Hongshan Yan, Ning Yu, Jianhui Zhao & Zongmao Zhao

  2. Department of Neonatology, Hebei Children’s Hospital, Shijiazhuang, Hebei, China

    Wenna Qiu

  3. Shandong Qilu Cell Therapy Engineering Technology Co., Ltd. Jinan, Shandong, China

    Yi Tan

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  1. Yanwei Fang
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  2. Wenna Qiu
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  3. Xin Li
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  4. Qianxu Jin
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  5. Hongshan Yan
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Contributions

Conception and study design, YF, WQ, SK, and ZZ; data collection, YF, WQ, SK, NY, XL, QJ, HY, JZ; data analysis and interpretation, YF, WQ, SK, XL, and ZZ; collection of materials and samples, NY, JZ, YT and YF; drafting manuscript, YF, WQ, SK, NY, XL, and ZZ; all the authors have read and approved the final manuscript.

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Correspondence to Zongmao Zhao.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

The experimental procedure was approved by the Animal Ethics Committee of Hebei Medical University (#SYXK (Hebei) 2018-008) and the Ethics Committee of The Second Hospital of Hebei Medical University (2018-R051).

Consent to participate

The experimental procedure was approved by the Animal Ethics Committee of Hebei Medical University (#SYXK (Hebei) 2018-008) and the Ethics Committee of The Second Hospital of Hebei Medical University (2018-R051).

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Not applicable.

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Communicated by Sreedharan Sajikumar.

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Fang, Y., Qiu, W., Li, X. et al. A combination of umbilical cord mesenchymal stem cells and monosialotetrahexosy 1 ganglioside alleviates neuroinflammation in traumatic brain injury. Exp Brain Res 241, 713–726 (2023). https://doi.org/10.1007/s00221-023-06554-4

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