Improvement of spinal cord injury symptoms by targeting the Bax/Bcl2 pathway and modulating TNF-α/IL-10 using Platelet-Rich Plasma exosomes loaded with dexamethasone

Naeimeh Akbari-Gharalari; Maryam Ghahremani-Nasab; Roya Naderi; Zeinab Aliyari-Serej; Mohammad Karimipour; Parviz Shahabi; Abbas Ebrahimi-Kalan; Naeimeh Akbari-Gharalari; Maryam Ghahremani-Nasab; Roya Naderi; Zeinab Aliyari-Serej; Mohammad Karimipour; Parviz Shahabi; Abbas Ebrahimi-Kalan

doi:10.3934/Neuroscience.2023026

AIMS Neuroscience

2023, Volume 10, Issue 4: 332-353. doi: 10.3934/Neuroscience.2023026

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Research article

Improvement of spinal cord injury symptoms by targeting the Bax/Bcl2 pathway and modulating TNF-α/IL-10 using Platelet-Rich Plasma exosomes loaded with dexamethasone

1.
Department of Neurosciences and Cognition, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
2.
Department of Tissue Engineering, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
3.
Neurophysiology Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
4.
Department of Physiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
5.
Department of Applied Cell Sciences, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
6.
Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
7.
Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
8.
Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Received: 26 September 2023 Revised: 12 November 2023 Accepted: 16 November 2023 Published: 20 November 2023

Spinal cord injury (SCI) is a debilitating condition that results in impaired sensory and motor function due to the limited self-regenerative ability of the spinal cord. To address this issue, combination therapy has been proposed as an effective treatment strategy for SCI regeneration. In this study, Platelet-Rich Plasma (PRP)-derived exosomes loaded with dexamethasone were utilized in a mouse model of SCI compression. PRP-derived exosomes loaded with dexamethasone (Dex) were prepared using ultracentrifugation and sonication methods and were administered to the mice via intravenous injection. Following a four-week duration, behavioral assessments were administered to assess functional recuperation, and diverse metrics encompassing the expression of genes associated with apoptosis and antiapoptosis, serum cytokine concentrations and tissue sampling were subjected to thorough examination. The results of this study demonstrated that mice treated with PRP-derived exosomes loaded with Dex (ExoDex) exhibited altered levels of TNF-α and IL-10, along with decreased Bax and increased Bcl2 expression in comparison to the model group. Furthermore, intravenously injected ExoDex reduced the size of the lesion site, lymphocyte infiltration, vacuolation, cavity size and tissue disorganization while also improving locomotor recovery. We propose that the utilization of exosome-loaded Dex therapy holds potential as a promising and clinically relevant approach for injured spinal cord repair. However, further extensive research is warranted in this domain to validate and substantiate the outcomes presented in this study.
- spinal cord injury,
- PRP-Derived exosome,
- dexamethasone,
- drug delivery,
- signaling pathways
Citation: Naeimeh Akbari-Gharalari, Maryam Ghahremani-Nasab, Roya Naderi, Zeinab Aliyari-Serej, Mohammad Karimipour, Parviz Shahabi, Abbas Ebrahimi-Kalan. Improvement of spinal cord injury symptoms by targeting the Bax/Bcl2 pathway and modulating TNF-α/IL-10 using Platelet-Rich Plasma exosomes loaded with dexamethasone[J]. AIMS Neuroscience, 2023, 10(4): 332-353. doi: 10.3934/Neuroscience.2023026

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Abstract

Spinal cord injury (SCI) is a debilitating condition that results in impaired sensory and motor function due to the limited self-regenerative ability of the spinal cord. To address this issue, combination therapy has been proposed as an effective treatment strategy for SCI regeneration. In this study, Platelet-Rich Plasma (PRP)-derived exosomes loaded with dexamethasone were utilized in a mouse model of SCI compression. PRP-derived exosomes loaded with dexamethasone (Dex) were prepared using ultracentrifugation and sonication methods and were administered to the mice via intravenous injection. Following a four-week duration, behavioral assessments were administered to assess functional recuperation, and diverse metrics encompassing the expression of genes associated with apoptosis and antiapoptosis, serum cytokine concentrations and tissue sampling were subjected to thorough examination. The results of this study demonstrated that mice treated with PRP-derived exosomes loaded with Dex (ExoDex) exhibited altered levels of TNF-α and IL-10, along with decreased Bax and increased Bcl2 expression in comparison to the model group. Furthermore, intravenously injected ExoDex reduced the size of the lesion site, lymphocyte infiltration, vacuolation, cavity size and tissue disorganization while also improving locomotor recovery. We propose that the utilization of exosome-loaded Dex therapy holds potential as a promising and clinically relevant approach for injured spinal cord repair. However, further extensive research is warranted in this domain to validate and substantiate the outcomes presented in this study.

Acknowledgments

The authors recognize the committed endeavors of the research personnel and collaborative contributors affiliated with Tabriz University of Medical Sciences, whose integral involvement was pivotal in both the meticulous acquisition of data and its subsequent analysis. Additionally, the authors express their specific gratitude to Dr. Farshad Nezhadshahmohammad, Dr. Hamid Soltani and Dr. Yahya Yahyavi for their noteworthy involvement in this venture. Their profound insights, specialized knowledge and persistent diligence significantly enhanced the quality and findings of this study.

Ethics approval and consent to participate

This investigation was conducted in accordance with the tenets of the Declaration of Helsinki and received authorization from the Ethics Committee of Tabriz University of Medical Sciences, located in Tabriz, Iran (Date: 20.02.2022, Protocol No. IR.TBZMED.AEC.1400.009).

Consent for publication

Not applicable.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Conflicts of interest

The authors declare that they have no competing interests.

Funding

The authors declare that no funds, grants or other support was received during the preparation of this manuscript.

Authors' contributions

All authors contributed to the study's conception and design. Abbas Ebrahimi-Kalan. conceptualized the content. Material preparation, data collection, analysis, design and generation of the figures by CorelDraw2021 were performed by Naeimeh Akbari-Gharalari. Maryam Ghahramani-Nasab, Roya Naderi, Zeinab Aliyari-Serej, Mohammad Karimipour, Parviz Shahabi and Abbas Ebrahimi-Kalan helped in the discussion and editing of the manuscript.

References

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