Activation of Neuroprotective Microglia and Astrocytes at the Lesion Site and in the Adjacent Segments Is Crucial for Spontaneous Locomotor Recovery after Spinal Cord Injury
Microglia and astrocytes play an important role in the regulation of immune responses under various pathological conditions. To detect environmental cues associated with the transformation of reactive microglia (M1) and astrocytes (A1) into their polarization states (anti-inflammatory M2 and A2 phen...
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MDPI AG
2021-07-01
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| author | Alexandra Kisucká Katarína Bimbová Mária Bačová Ján Gálik Nadežda Lukáčová |
| author_facet | Alexandra Kisucká Katarína Bimbová Mária Bačová Ján Gálik Nadežda Lukáčová |
| author_sort | Alexandra Kisucká |
| collection | DOAJ |
| description | Microglia and astrocytes play an important role in the regulation of immune responses under various pathological conditions. To detect environmental cues associated with the transformation of reactive microglia (M1) and astrocytes (A1) into their polarization states (anti-inflammatory M2 and A2 phenotypes), we studied time-dependent gene expression in naive and injured spinal cord. The relationship between astrocytes and microglia and their polarization states were studied in a rat model after Th9 compression (40 g/15 min) in acute and subacute stages at the lesion site, and both cranially and caudally. The gene expression of microglia/macrophages and M1 microglia was strongly up-regulated at the lesion site and caudally one week after SCI, and attenuated after two weeks post-SCI. GFAP and S100B, and A1 astrocytes were profoundly expressed predominantly two weeks post-SCI at lesion site and cranially. Gene expression of anti-inflammatory M2a microglia (CD206, CHICHI, IL1rn, Arg-1), M2c microglia (TGF-β, SOCS3, IL4R α) and A2 astrocytes (Tgm1, Ptx3, CD109) was greatly activated at the lesion site one week post-SCI. In addition, we observed positive correlation between neurological outcome and expression of M2a, M2c, and A2 markers. Our findings indicate that the first week post-injury is critical for modulation of reactive microglia/astrocytes into their neuroprotective phenotypes. |
| first_indexed | 2024-03-10T08:55:43Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T08:55:43Z |
| publishDate | 2021-07-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-9eabf4bf0b7e4425bd4e69f5676739fb2023-11-22T07:09:30ZengMDPI AGCells2073-44092021-07-01108194310.3390/cells10081943Activation of Neuroprotective Microglia and Astrocytes at the Lesion Site and in the Adjacent Segments Is Crucial for Spontaneous Locomotor Recovery after Spinal Cord InjuryAlexandra Kisucká0Katarína Bimbová1Mária Bačová2Ján Gálik3Nadežda Lukáčová4Institute of Neurobiology of Biomedical Research Centre of Slovak Academy of Sciences, Soltesovej 4, 040 01 Kosice, SlovakiaInstitute of Neurobiology of Biomedical Research Centre of Slovak Academy of Sciences, Soltesovej 4, 040 01 Kosice, SlovakiaInstitute of Neurobiology of Biomedical Research Centre of Slovak Academy of Sciences, Soltesovej 4, 040 01 Kosice, SlovakiaInstitute of Neurobiology of Biomedical Research Centre of Slovak Academy of Sciences, Soltesovej 4, 040 01 Kosice, SlovakiaInstitute of Neurobiology of Biomedical Research Centre of Slovak Academy of Sciences, Soltesovej 4, 040 01 Kosice, SlovakiaMicroglia and astrocytes play an important role in the regulation of immune responses under various pathological conditions. To detect environmental cues associated with the transformation of reactive microglia (M1) and astrocytes (A1) into their polarization states (anti-inflammatory M2 and A2 phenotypes), we studied time-dependent gene expression in naive and injured spinal cord. The relationship between astrocytes and microglia and their polarization states were studied in a rat model after Th9 compression (40 g/15 min) in acute and subacute stages at the lesion site, and both cranially and caudally. The gene expression of microglia/macrophages and M1 microglia was strongly up-regulated at the lesion site and caudally one week after SCI, and attenuated after two weeks post-SCI. GFAP and S100B, and A1 astrocytes were profoundly expressed predominantly two weeks post-SCI at lesion site and cranially. Gene expression of anti-inflammatory M2a microglia (CD206, CHICHI, IL1rn, Arg-1), M2c microglia (TGF-β, SOCS3, IL4R α) and A2 astrocytes (Tgm1, Ptx3, CD109) was greatly activated at the lesion site one week post-SCI. In addition, we observed positive correlation between neurological outcome and expression of M2a, M2c, and A2 markers. Our findings indicate that the first week post-injury is critical for modulation of reactive microglia/astrocytes into their neuroprotective phenotypes.https://www.mdpi.com/2073-4409/10/8/1943microglia/macrophagesmicroglial phenotypes: M1M2a and M2cA1 and A2 reactive astrocytesTh9 compressiongene expression |
| spellingShingle | Alexandra Kisucká Katarína Bimbová Mária Bačová Ján Gálik Nadežda Lukáčová Activation of Neuroprotective Microglia and Astrocytes at the Lesion Site and in the Adjacent Segments Is Crucial for Spontaneous Locomotor Recovery after Spinal Cord Injury Cells microglia/macrophages microglial phenotypes: M1 M2a and M2c A1 and A2 reactive astrocytes Th9 compression gene expression |
| title | Activation of Neuroprotective Microglia and Astrocytes at the Lesion Site and in the Adjacent Segments Is Crucial for Spontaneous Locomotor Recovery after Spinal Cord Injury |
| title_full | Activation of Neuroprotective Microglia and Astrocytes at the Lesion Site and in the Adjacent Segments Is Crucial for Spontaneous Locomotor Recovery after Spinal Cord Injury |
| title_fullStr | Activation of Neuroprotective Microglia and Astrocytes at the Lesion Site and in the Adjacent Segments Is Crucial for Spontaneous Locomotor Recovery after Spinal Cord Injury |
| title_full_unstemmed | Activation of Neuroprotective Microglia and Astrocytes at the Lesion Site and in the Adjacent Segments Is Crucial for Spontaneous Locomotor Recovery after Spinal Cord Injury |
| title_short | Activation of Neuroprotective Microglia and Astrocytes at the Lesion Site and in the Adjacent Segments Is Crucial for Spontaneous Locomotor Recovery after Spinal Cord Injury |
| title_sort | activation of neuroprotective microglia and astrocytes at the lesion site and in the adjacent segments is crucial for spontaneous locomotor recovery after spinal cord injury |
| topic | microglia/macrophages microglial phenotypes: M1 M2a and M2c A1 and A2 reactive astrocytes Th9 compression gene expression |
| url | https://www.mdpi.com/2073-4409/10/8/1943 |
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