HDAC8 Inhibition Reduces Lesional Iba-1+ Cell Infiltration after Spinal Cord Injury without Effects on Functional Recovery
Pan-histone deacetylase (HDAC) inhibition with valproic acid (VPA) has beneficial effects after spinal cord injury (SCI), although with side effects. We focused on specific HDAC8 inhibition, because it is known to reduce anti-inflammatory mediators produced by macrophages (Mφ). We hypothesized that...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/12/4539 |
| _version_ | 1797564135081246720 |
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| author | Sven Hendrix Selien Sanchez Elissia Ventriglia Stefanie Lemmens |
| author_facet | Sven Hendrix Selien Sanchez Elissia Ventriglia Stefanie Lemmens |
| author_sort | Sven Hendrix |
| collection | DOAJ |
| description | Pan-histone deacetylase (HDAC) inhibition with valproic acid (VPA) has beneficial effects after spinal cord injury (SCI), although with side effects. We focused on specific HDAC8 inhibition, because it is known to reduce anti-inflammatory mediators produced by macrophages (Mφ). We hypothesized that HDAC8 inhibition improves functional recovery after SCI by reducing pro-inflammatory classically activated Mφ. Specific HDAC8 inhibition with PCI-34051 reduced the numbers of perilesional Mφ as measured by histological analyses, but did not improve functional recovery (Basso Mouse Scale). We could not reproduce the published improvement of functional recovery described in contusion SCI models using VPA in our T-cut hemisection SCI model. The presence of spared fibers might be the underlying reason for the conflicting data in different SCI models. |
| first_indexed | 2024-03-10T18:53:07Z |
| format | Article |
| id | doaj.art-3838a60d65b94de8a279a67dcdebe523 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:53:07Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3838a60d65b94de8a279a67dcdebe5232023-11-20T04:59:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-012112453910.3390/ijms21124539HDAC8 Inhibition Reduces Lesional Iba-1+ Cell Infiltration after Spinal Cord Injury without Effects on Functional RecoverySven Hendrix0Selien Sanchez1Elissia Ventriglia2Stefanie Lemmens3Department of Immunology, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, BelgiumDepartment of Immunology, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, BelgiumDepartment of Immunology, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, BelgiumDepartment of Immunology, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, BelgiumPan-histone deacetylase (HDAC) inhibition with valproic acid (VPA) has beneficial effects after spinal cord injury (SCI), although with side effects. We focused on specific HDAC8 inhibition, because it is known to reduce anti-inflammatory mediators produced by macrophages (Mφ). We hypothesized that HDAC8 inhibition improves functional recovery after SCI by reducing pro-inflammatory classically activated Mφ. Specific HDAC8 inhibition with PCI-34051 reduced the numbers of perilesional Mφ as measured by histological analyses, but did not improve functional recovery (Basso Mouse Scale). We could not reproduce the published improvement of functional recovery described in contusion SCI models using VPA in our T-cut hemisection SCI model. The presence of spared fibers might be the underlying reason for the conflicting data in different SCI models.https://www.mdpi.com/1422-0067/21/12/4539HDAC inhibitionPCI-34051valproic acid |
| spellingShingle | Sven Hendrix Selien Sanchez Elissia Ventriglia Stefanie Lemmens HDAC8 Inhibition Reduces Lesional Iba-1+ Cell Infiltration after Spinal Cord Injury without Effects on Functional Recovery International Journal of Molecular Sciences HDAC inhibition PCI-34051 valproic acid |
| title | HDAC8 Inhibition Reduces Lesional Iba-1+ Cell Infiltration after Spinal Cord Injury without Effects on Functional Recovery |
| title_full | HDAC8 Inhibition Reduces Lesional Iba-1+ Cell Infiltration after Spinal Cord Injury without Effects on Functional Recovery |
| title_fullStr | HDAC8 Inhibition Reduces Lesional Iba-1+ Cell Infiltration after Spinal Cord Injury without Effects on Functional Recovery |
| title_full_unstemmed | HDAC8 Inhibition Reduces Lesional Iba-1+ Cell Infiltration after Spinal Cord Injury without Effects on Functional Recovery |
| title_short | HDAC8 Inhibition Reduces Lesional Iba-1+ Cell Infiltration after Spinal Cord Injury without Effects on Functional Recovery |
| title_sort | hdac8 inhibition reduces lesional iba 1 cell infiltration after spinal cord injury without effects on functional recovery |
| topic | HDAC inhibition PCI-34051 valproic acid |
| url | https://www.mdpi.com/1422-0067/21/12/4539 |
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