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Methylprednisolone Induces Neuro-Protective Effects via the Inhibition of A1 Astrocyte Activation in Traumatic Spinal Cord Injury Mouse Models

Traumatic spinal cord injury (TSCI) leads to pathological changes such as inflammation, edema, and neuronal apoptosis. Methylprednisolone (MP) is a glucocorticoid that has a variety of beneficial effects, including decreasing inflammation and ischemic reaction, as well as inhibiting lipid peroxidati...

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Autores principales: Zou, Hong-jun, Guo, Shi-Wu, Zhu, Lin, Xu, Xu, Liu, Jin-bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200570/
https://www.ncbi.nlm.nih.gov/pubmed/34135725
http://dx.doi.org/10.3389/fnins.2021.628917
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author Zou, Hong-jun
Guo, Shi-Wu
Zhu, Lin
Xu, Xu
Liu, Jin-bo
author_facet Zou, Hong-jun
Guo, Shi-Wu
Zhu, Lin
Xu, Xu
Liu, Jin-bo
author_sort Zou, Hong-jun
collection PubMed
description Traumatic spinal cord injury (TSCI) leads to pathological changes such as inflammation, edema, and neuronal apoptosis. Methylprednisolone (MP) is a glucocorticoid that has a variety of beneficial effects, including decreasing inflammation and ischemic reaction, as well as inhibiting lipid peroxidation. However, the efficacy and mechanism of MP in TSCI therapy is yet to be deciphered. In the present study, MP significantly attenuated the apoptotic effects of H(2)O(2) in neuronal cells. Western blot analysis demonstrated that the levels of apoptotic related proteins, Bax and cleaved caspase-3, were reduced while levels of anti-apoptotic Bcl-2 were increased. In vivo TUNEL assays further demonstrated that MP effectively protected neuronal cells from apoptosis after TSCI, and was consistent with in vitro studies. Furthermore, we demonstrated that MP could decrease expression levels of IBA1, Il-1α, TNFα, and C3 and suppress A1 neurotoxic reactive astrocyte activation in TSCI mouse models. Neurological function was evaluated using the Basso Mouse Scale (BMS) and Footprint Test. Results demonstrated that the neurological function of MP-treated injured mice was significantly increased. In conclusion, our study demonstrated that MP could attenuate astrocyte cell death, decrease microglia activation, suppress A1 astrocytes activation, and promote functional recovery after acute TSCI in mouse models.
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spelling pubmed-82005702021-06-15 Methylprednisolone Induces Neuro-Protective Effects via the Inhibition of A1 Astrocyte Activation in Traumatic Spinal Cord Injury Mouse Models Zou, Hong-jun Guo, Shi-Wu Zhu, Lin Xu, Xu Liu, Jin-bo Front Neurosci Neuroscience Traumatic spinal cord injury (TSCI) leads to pathological changes such as inflammation, edema, and neuronal apoptosis. Methylprednisolone (MP) is a glucocorticoid that has a variety of beneficial effects, including decreasing inflammation and ischemic reaction, as well as inhibiting lipid peroxidation. However, the efficacy and mechanism of MP in TSCI therapy is yet to be deciphered. In the present study, MP significantly attenuated the apoptotic effects of H(2)O(2) in neuronal cells. Western blot analysis demonstrated that the levels of apoptotic related proteins, Bax and cleaved caspase-3, were reduced while levels of anti-apoptotic Bcl-2 were increased. In vivo TUNEL assays further demonstrated that MP effectively protected neuronal cells from apoptosis after TSCI, and was consistent with in vitro studies. Furthermore, we demonstrated that MP could decrease expression levels of IBA1, Il-1α, TNFα, and C3 and suppress A1 neurotoxic reactive astrocyte activation in TSCI mouse models. Neurological function was evaluated using the Basso Mouse Scale (BMS) and Footprint Test. Results demonstrated that the neurological function of MP-treated injured mice was significantly increased. In conclusion, our study demonstrated that MP could attenuate astrocyte cell death, decrease microglia activation, suppress A1 astrocytes activation, and promote functional recovery after acute TSCI in mouse models. Frontiers Media S.A. 2021-05-31 /pmc/articles/PMC8200570/ /pubmed/34135725 http://dx.doi.org/10.3389/fnins.2021.628917 Text en Copyright © 2021 Zou, Guo, Zhu, Xu and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Zou, Hong-jun
Guo, Shi-Wu
Zhu, Lin
Xu, Xu
Liu, Jin-bo
Methylprednisolone Induces Neuro-Protective Effects via the Inhibition of A1 Astrocyte Activation in Traumatic Spinal Cord Injury Mouse Models
title Methylprednisolone Induces Neuro-Protective Effects via the Inhibition of A1 Astrocyte Activation in Traumatic Spinal Cord Injury Mouse Models
title_full Methylprednisolone Induces Neuro-Protective Effects via the Inhibition of A1 Astrocyte Activation in Traumatic Spinal Cord Injury Mouse Models
title_fullStr Methylprednisolone Induces Neuro-Protective Effects via the Inhibition of A1 Astrocyte Activation in Traumatic Spinal Cord Injury Mouse Models
title_full_unstemmed Methylprednisolone Induces Neuro-Protective Effects via the Inhibition of A1 Astrocyte Activation in Traumatic Spinal Cord Injury Mouse Models
title_short Methylprednisolone Induces Neuro-Protective Effects via the Inhibition of A1 Astrocyte Activation in Traumatic Spinal Cord Injury Mouse Models
title_sort methylprednisolone induces neuro-protective effects via the inhibition of a1 astrocyte activation in traumatic spinal cord injury mouse models
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200570/
https://www.ncbi.nlm.nih.gov/pubmed/34135725
http://dx.doi.org/10.3389/fnins.2021.628917
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