The Role of Microglia/Macrophages Activation and TLR4/NF-κB/MAPK Pathway in Distraction Spinal Cord Injury-Induced Inflammation
Distraction spinal cord injuries (DSCIs) often occur as the neurological complication of distraction forces following the implantation of internal fixation devices during scoliosis correction surgery. However, the underlying mechanism behind these injuries remains unclear. The present study aimed to...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-06-01
|
| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2022.926453/full |
| _version_ | 1818552760330616832 |
|---|---|
| author | Weishi Liang Bo Han Yong Hai Yuzeng Liu Xing Liu Jincai Yang Duan Sun Peng Yin |
| author_facet | Weishi Liang Bo Han Yong Hai Yuzeng Liu Xing Liu Jincai Yang Duan Sun Peng Yin |
| author_sort | Weishi Liang |
| collection | DOAJ |
| description | Distraction spinal cord injuries (DSCIs) often occur as the neurological complication of distraction forces following the implantation of internal fixation devices during scoliosis correction surgery. However, the underlying mechanism behind these injuries remains unclear. The present study aimed to explore the activation of microglia and macrophages, as well as changes in TLR4-mediated NF-κB and MAPK pathway activity after DSCIs in Bama miniature pigs. Prior to surgical intervention, the pigs were randomly divided into three groups: the sham group, the complete distraction spinal cord injury (CDSCI) group, and the incomplete distraction spinal cord injury (IDSCI) group. After surgery, the Tarlov scale and individual limb motor scale (ILMS) were used to evaluate changes in the pigs’ behavior. All pigs were euthanized 7 days after surgery, and histopathological examinations of the spinal cord tissues were performed. Immunohistochemistry was used to detect Caspase-3 expression in the anterior horn of spinal gray matter tissues. Immunofluorescence staining was utilized to assess the M1/M2 phenotype changes in microglia/macrophages and NF-κB P65 expression in central DSCI lesions, while western blotting was performed to determine the expression of TLR4/NF-κB/MAPK pathway-related proteins. The results of the present study showed that the Tarlov and ILMS scores decreased significantly in the two DSCI groups compared with the sham group. Hematoxylin and eosin (HE) and Nissl staining revealed that the tissue structure and nerve fiber tracts in the distracted spinal cord tissues were destroyed. Both DSCI groups showed the number of survived neurons decreased and the Caspase-3 expression increased. The results of the immunofluorescence staining indicated that the CD16 and CD206 expression in the microglia/macrophages increased. Between the two DSCI groups, the CDSCI group showed increased CD16 and decreased CD206 expression levels. The intensity of the fluorescence of NF-κB P65 was found to be significantly enhanced in pigs with DSCIs. Moreover, western blot results revealed that the expression of TLR4, p-IκBα, NF-κB P65, p-JNK, p-ERK, and p-P38 proteins increased in spinal cord tissues following DSCI. The present study was based on a porcine DSCI model that closely mimicked clinical DSCIs while clarifying DSCI-associated neuroinflammation mechanisms, in turn providing evidence for identifying potential anti-inflammatory targets. |
| first_indexed | 2024-12-12T09:17:23Z |
| format | Article |
| id | doaj.art-8d5887d13a3b4b14953dd898d0c8cd36 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-12T09:17:23Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-8d5887d13a3b4b14953dd898d0c8cd362022-12-22T00:29:20ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022022-06-011610.3389/fncel.2022.926453926453The Role of Microglia/Macrophages Activation and TLR4/NF-κB/MAPK Pathway in Distraction Spinal Cord Injury-Induced InflammationWeishi Liang0Bo Han1Yong Hai2Yuzeng Liu3Xing Liu4Jincai Yang5Duan Sun6Peng Yin7Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDistraction spinal cord injuries (DSCIs) often occur as the neurological complication of distraction forces following the implantation of internal fixation devices during scoliosis correction surgery. However, the underlying mechanism behind these injuries remains unclear. The present study aimed to explore the activation of microglia and macrophages, as well as changes in TLR4-mediated NF-κB and MAPK pathway activity after DSCIs in Bama miniature pigs. Prior to surgical intervention, the pigs were randomly divided into three groups: the sham group, the complete distraction spinal cord injury (CDSCI) group, and the incomplete distraction spinal cord injury (IDSCI) group. After surgery, the Tarlov scale and individual limb motor scale (ILMS) were used to evaluate changes in the pigs’ behavior. All pigs were euthanized 7 days after surgery, and histopathological examinations of the spinal cord tissues were performed. Immunohistochemistry was used to detect Caspase-3 expression in the anterior horn of spinal gray matter tissues. Immunofluorescence staining was utilized to assess the M1/M2 phenotype changes in microglia/macrophages and NF-κB P65 expression in central DSCI lesions, while western blotting was performed to determine the expression of TLR4/NF-κB/MAPK pathway-related proteins. The results of the present study showed that the Tarlov and ILMS scores decreased significantly in the two DSCI groups compared with the sham group. Hematoxylin and eosin (HE) and Nissl staining revealed that the tissue structure and nerve fiber tracts in the distracted spinal cord tissues were destroyed. Both DSCI groups showed the number of survived neurons decreased and the Caspase-3 expression increased. The results of the immunofluorescence staining indicated that the CD16 and CD206 expression in the microglia/macrophages increased. Between the two DSCI groups, the CDSCI group showed increased CD16 and decreased CD206 expression levels. The intensity of the fluorescence of NF-κB P65 was found to be significantly enhanced in pigs with DSCIs. Moreover, western blot results revealed that the expression of TLR4, p-IκBα, NF-κB P65, p-JNK, p-ERK, and p-P38 proteins increased in spinal cord tissues following DSCI. The present study was based on a porcine DSCI model that closely mimicked clinical DSCIs while clarifying DSCI-associated neuroinflammation mechanisms, in turn providing evidence for identifying potential anti-inflammatory targets.https://www.frontiersin.org/articles/10.3389/fncel.2022.926453/fulldistraction spinal cord injurymicroglia/macrophagesneuroinflammationTLR4 signaling pathwayporcine model |
| spellingShingle | Weishi Liang Bo Han Yong Hai Yuzeng Liu Xing Liu Jincai Yang Duan Sun Peng Yin The Role of Microglia/Macrophages Activation and TLR4/NF-κB/MAPK Pathway in Distraction Spinal Cord Injury-Induced Inflammation Frontiers in Cellular Neuroscience distraction spinal cord injury microglia/macrophages neuroinflammation TLR4 signaling pathway porcine model |
| title | The Role of Microglia/Macrophages Activation and TLR4/NF-κB/MAPK Pathway in Distraction Spinal Cord Injury-Induced Inflammation |
| title_full | The Role of Microglia/Macrophages Activation and TLR4/NF-κB/MAPK Pathway in Distraction Spinal Cord Injury-Induced Inflammation |
| title_fullStr | The Role of Microglia/Macrophages Activation and TLR4/NF-κB/MAPK Pathway in Distraction Spinal Cord Injury-Induced Inflammation |
| title_full_unstemmed | The Role of Microglia/Macrophages Activation and TLR4/NF-κB/MAPK Pathway in Distraction Spinal Cord Injury-Induced Inflammation |
| title_short | The Role of Microglia/Macrophages Activation and TLR4/NF-κB/MAPK Pathway in Distraction Spinal Cord Injury-Induced Inflammation |
| title_sort | role of microglia macrophages activation and tlr4 nf κb mapk pathway in distraction spinal cord injury induced inflammation |
| topic | distraction spinal cord injury microglia/macrophages neuroinflammation TLR4 signaling pathway porcine model |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2022.926453/full |
| work_keys_str_mv | AT weishiliang theroleofmicrogliamacrophagesactivationandtlr4nfkbmapkpathwayindistractionspinalcordinjuryinducedinflammation AT bohan theroleofmicrogliamacrophagesactivationandtlr4nfkbmapkpathwayindistractionspinalcordinjuryinducedinflammation AT yonghai theroleofmicrogliamacrophagesactivationandtlr4nfkbmapkpathwayindistractionspinalcordinjuryinducedinflammation AT yuzengliu theroleofmicrogliamacrophagesactivationandtlr4nfkbmapkpathwayindistractionspinalcordinjuryinducedinflammation AT xingliu theroleofmicrogliamacrophagesactivationandtlr4nfkbmapkpathwayindistractionspinalcordinjuryinducedinflammation AT jincaiyang theroleofmicrogliamacrophagesactivationandtlr4nfkbmapkpathwayindistractionspinalcordinjuryinducedinflammation AT duansun theroleofmicrogliamacrophagesactivationandtlr4nfkbmapkpathwayindistractionspinalcordinjuryinducedinflammation AT pengyin theroleofmicrogliamacrophagesactivationandtlr4nfkbmapkpathwayindistractionspinalcordinjuryinducedinflammation AT weishiliang roleofmicrogliamacrophagesactivationandtlr4nfkbmapkpathwayindistractionspinalcordinjuryinducedinflammation AT bohan roleofmicrogliamacrophagesactivationandtlr4nfkbmapkpathwayindistractionspinalcordinjuryinducedinflammation AT yonghai roleofmicrogliamacrophagesactivationandtlr4nfkbmapkpathwayindistractionspinalcordinjuryinducedinflammation AT yuzengliu roleofmicrogliamacrophagesactivationandtlr4nfkbmapkpathwayindistractionspinalcordinjuryinducedinflammation AT xingliu roleofmicrogliamacrophagesactivationandtlr4nfkbmapkpathwayindistractionspinalcordinjuryinducedinflammation AT jincaiyang roleofmicrogliamacrophagesactivationandtlr4nfkbmapkpathwayindistractionspinalcordinjuryinducedinflammation AT duansun roleofmicrogliamacrophagesactivationandtlr4nfkbmapkpathwayindistractionspinalcordinjuryinducedinflammation AT pengyin roleofmicrogliamacrophagesactivationandtlr4nfkbmapkpathwayindistractionspinalcordinjuryinducedinflammation |