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Elucidating the Potential Mechanisms Underlying Distraction Spinal Cord Injury-Associated Neuroinflammation and Apoptosis

The incidence of distraction spinal cord injury (DSCI), which results from spinal cord ischemia due to vascular compromise and spinal cord tract disturbances, remains high. Furthermore, because no ideal animal model that mimics DSCI in clinical settings is available thus far, the related molecular m...

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Autores principales: Han, Bo, Liang, Weishi, Hai, Yong, Liu, Yuzeng, Chen, Yuxiang, Ding, Hongtao, Yang, Jincai, Yin, Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8898939/
https://www.ncbi.nlm.nih.gov/pubmed/35265624
http://dx.doi.org/10.3389/fcell.2022.839313
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author Han, Bo
Liang, Weishi
Hai, Yong
Liu, Yuzeng
Chen, Yuxiang
Ding, Hongtao
Yang, Jincai
Yin, Peng
author_facet Han, Bo
Liang, Weishi
Hai, Yong
Liu, Yuzeng
Chen, Yuxiang
Ding, Hongtao
Yang, Jincai
Yin, Peng
author_sort Han, Bo
collection PubMed
description The incidence of distraction spinal cord injury (DSCI), which results from spinal cord ischemia due to vascular compromise and spinal cord tract disturbances, remains high. Furthermore, because no ideal animal model that mimics DSCI in clinical settings is available thus far, the related molecular mechanisms underlying DSCI remain unclear. Thus, this study aimed to establish a porcine model of DSCI and investigate the neuroinflammation and apoptosis mechanisms in these pigs. Before surgery, all pigs were randomly divided into three groups: sham group, osteotomy surgery only; the incomplete distraction spinal cord injury (IDSCI) and complete distraction spinal cord injury (CDSCI) group, osteotomy plus DSCI surgery with a motor-evoked potential (MEP) amplitude decreased by approximately 75% and 100%, respectively. After surgery, modified Tarlov scoring and MRC muscle strength scoring were used to evaluate neurologic function in each group. We observed the distracted spinal cord using MRI, and then all pigs were sacrificed. Inflammatory cytokine levels in the spinal cord and cerebrospinal fluid (CSF) were also analyzed. We used immunofluorescence staining to assess the neuronal and microglial structure and function and astrocyte hyperplasia in the central DSCI lesions (T15). Western blotting was used to determine the expression of apoptosis-related proteins. Results showed that the modified Tarlov scoring and muscle strength decreased significantly in the two DSCI groups. T2-MRI showed a relative enhancement at the center of the DSCI lesions. H&E and Lxol fast blue staining revealed that spinal cord distraction destroyed the normal structure of spinal cord tissues and nerve fiber tracts, exacerbating inflammatory cell infiltration, hyperemia, and edema. The IL-1β, IL-6, and TNF-α levels increased in the spinal cord and CSF following DSCI. Immunofluorescence staining results indicated the GFAP, Iba-1 expression increased following DSCI, whereas the NeuN expression reduced. Moreover, DSCI promoted the protein expression of P53, Bcl-2-associated X protein (Bax), and Caspase-3 in the spinal cord tissues, whereas it reduced the Bcl-2 expression. This study successfully established a porcine DSCI model that closely mimics DSCI in clinical settings, and clarified the mechanisms underlying DSCI-associated neuroinflammation and apoptosis; thus, our findings highlight potential DSCI-treatment strategies for further establishing suitable drug therapies.
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spelling pubmed-88989392022-03-08 Elucidating the Potential Mechanisms Underlying Distraction Spinal Cord Injury-Associated Neuroinflammation and Apoptosis Han, Bo Liang, Weishi Hai, Yong Liu, Yuzeng Chen, Yuxiang Ding, Hongtao Yang, Jincai Yin, Peng Front Cell Dev Biol Cell and Developmental Biology The incidence of distraction spinal cord injury (DSCI), which results from spinal cord ischemia due to vascular compromise and spinal cord tract disturbances, remains high. Furthermore, because no ideal animal model that mimics DSCI in clinical settings is available thus far, the related molecular mechanisms underlying DSCI remain unclear. Thus, this study aimed to establish a porcine model of DSCI and investigate the neuroinflammation and apoptosis mechanisms in these pigs. Before surgery, all pigs were randomly divided into three groups: sham group, osteotomy surgery only; the incomplete distraction spinal cord injury (IDSCI) and complete distraction spinal cord injury (CDSCI) group, osteotomy plus DSCI surgery with a motor-evoked potential (MEP) amplitude decreased by approximately 75% and 100%, respectively. After surgery, modified Tarlov scoring and MRC muscle strength scoring were used to evaluate neurologic function in each group. We observed the distracted spinal cord using MRI, and then all pigs were sacrificed. Inflammatory cytokine levels in the spinal cord and cerebrospinal fluid (CSF) were also analyzed. We used immunofluorescence staining to assess the neuronal and microglial structure and function and astrocyte hyperplasia in the central DSCI lesions (T15). Western blotting was used to determine the expression of apoptosis-related proteins. Results showed that the modified Tarlov scoring and muscle strength decreased significantly in the two DSCI groups. T2-MRI showed a relative enhancement at the center of the DSCI lesions. H&E and Lxol fast blue staining revealed that spinal cord distraction destroyed the normal structure of spinal cord tissues and nerve fiber tracts, exacerbating inflammatory cell infiltration, hyperemia, and edema. The IL-1β, IL-6, and TNF-α levels increased in the spinal cord and CSF following DSCI. Immunofluorescence staining results indicated the GFAP, Iba-1 expression increased following DSCI, whereas the NeuN expression reduced. Moreover, DSCI promoted the protein expression of P53, Bcl-2-associated X protein (Bax), and Caspase-3 in the spinal cord tissues, whereas it reduced the Bcl-2 expression. This study successfully established a porcine DSCI model that closely mimics DSCI in clinical settings, and clarified the mechanisms underlying DSCI-associated neuroinflammation and apoptosis; thus, our findings highlight potential DSCI-treatment strategies for further establishing suitable drug therapies. Frontiers Media S.A. 2022-02-21 /pmc/articles/PMC8898939/ /pubmed/35265624 http://dx.doi.org/10.3389/fcell.2022.839313 Text en Copyright © 2022 Han, Liang, Hai, Liu, Chen, Ding, Yang and Yin. 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 Cell and Developmental Biology
Han, Bo
Liang, Weishi
Hai, Yong
Liu, Yuzeng
Chen, Yuxiang
Ding, Hongtao
Yang, Jincai
Yin, Peng
Elucidating the Potential Mechanisms Underlying Distraction Spinal Cord Injury-Associated Neuroinflammation and Apoptosis
title Elucidating the Potential Mechanisms Underlying Distraction Spinal Cord Injury-Associated Neuroinflammation and Apoptosis
title_full Elucidating the Potential Mechanisms Underlying Distraction Spinal Cord Injury-Associated Neuroinflammation and Apoptosis
title_fullStr Elucidating the Potential Mechanisms Underlying Distraction Spinal Cord Injury-Associated Neuroinflammation and Apoptosis
title_full_unstemmed Elucidating the Potential Mechanisms Underlying Distraction Spinal Cord Injury-Associated Neuroinflammation and Apoptosis
title_short Elucidating the Potential Mechanisms Underlying Distraction Spinal Cord Injury-Associated Neuroinflammation and Apoptosis
title_sort elucidating the potential mechanisms underlying distraction spinal cord injury-associated neuroinflammation and apoptosis
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8898939/
https://www.ncbi.nlm.nih.gov/pubmed/35265624
http://dx.doi.org/10.3389/fcell.2022.839313
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