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

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 stud...

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Main Authors: Naeimeh Akbari-Gharalari, Maryam Ghahremani-Nasab, Roya Naderi, Zeinab Aliyari-Serej, Mohammad Karimipour, Parviz Shahabi, Abbas Ebrahimi-Kalan
Format: Article
Language:English
Published: AIMS Press 2023-11-01
Series:AIMS Neuroscience
Subjects:
Online Access:https://www.aimspress.com/article/doi/10.3934/Neuroscience.2023026?viewType=HTML
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author Naeimeh Akbari-Gharalari
Maryam Ghahremani-Nasab
Roya Naderi
Zeinab Aliyari-Serej
Mohammad Karimipour
Parviz Shahabi
Abbas Ebrahimi-Kalan
author_facet Naeimeh Akbari-Gharalari
Maryam Ghahremani-Nasab
Roya Naderi
Zeinab Aliyari-Serej
Mohammad Karimipour
Parviz Shahabi
Abbas Ebrahimi-Kalan
author_sort Naeimeh Akbari-Gharalari
collection DOAJ
description 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.
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spelling doaj.art-58cd48a79f7744faafc3709266fcd72a2024-01-04T01:17:17ZengAIMS PressAIMS Neuroscience2373-79722023-11-0110433235310.3934/Neuroscience.2023026Improvement of spinal cord injury symptoms by targeting the Bax/Bcl2 pathway and modulating TNF-α/IL-10 using Platelet-Rich Plasma exosomes loaded with dexamethasoneNaeimeh Akbari-Gharalari0Maryam Ghahremani-Nasab 1Roya Naderi 2Zeinab Aliyari-Serej3Mohammad Karimipour4 Parviz Shahabi5Abbas Ebrahimi-Kalan61. Department of Neurosciences and Cognition, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran2. Department of Tissue Engineering, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran3. 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, Iran5. Department of Applied Cell Sciences, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran6. Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran8. Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran7. Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran 8. Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran1. Department of Neurosciences and Cognition, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran8. Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, IranSpinal 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.https://www.aimspress.com/article/doi/10.3934/Neuroscience.2023026?viewType=HTMLspinal cord injuryprp-derived exosomedexamethasonedrug deliverysignaling pathways
spellingShingle 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
AIMS Neuroscience
spinal cord injury
prp-derived exosome
dexamethasone
drug delivery
signaling pathways
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic spinal cord injury
prp-derived exosome
dexamethasone
drug delivery
signaling pathways
url https://www.aimspress.com/article/doi/10.3934/Neuroscience.2023026?viewType=HTML
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