Cargando…
Valproic acid attenuates intercellular adhesion molecule-1 and E-selectin through a chemokine ligand 5 dependent mechanism and subarachnoid hemorrhage induced vasospasm in a rat model
BACKGROUND: Up-regulation of regulated upon activation, normal T-cell expressed and secreted (RANTES/CCL5) and adhesion molecules is observed in the serum of animals following experimental subarachnoid hemorrhage (SAH). The present study was to examine the effect of valproic acid (VPA) on RANTES and...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407545/ https://www.ncbi.nlm.nih.gov/pubmed/25908928 http://dx.doi.org/10.1186/s12950-015-0074-3 |
_version_ | 1782367926902325248 |
---|---|
author | Chang, Chih-Zen Wu, Shu-Chuan Lin, Chih-Lung Kwan, Aij-Lie |
author_facet | Chang, Chih-Zen Wu, Shu-Chuan Lin, Chih-Lung Kwan, Aij-Lie |
author_sort | Chang, Chih-Zen |
collection | PubMed |
description | BACKGROUND: Up-regulation of regulated upon activation, normal T-cell expressed and secreted (RANTES/CCL5) and adhesion molecules is observed in the serum of animals following experimental subarachnoid hemorrhage (SAH). The present study was to examine the effect of valproic acid (VPA) on RANTES and alternation of adhesion molecules in this model. METHODS: A rodent SAH model was employed. Animals were randomly assigned into six groups. Basilar artery (BA) was harvested for intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule–1 (VCAM-1), and E-selectin evaluation (western blotting) and RANTES (rt-PCR). 1 ng CCL5 recombinant protein intrathecal injection was performed in the VPA + SAH groups. (N = 5). RESULTS: Convoluted internal elastic lamina, distorted endothelial wall, and smooth muscle micro-necrosis was prominently observed in the SAH groups, which is absent in the VPA treatment and the healthy controls. Treatment with VPA dose-dependently reduced the ICAM-1, E-selectin and RANTES level, compared with the SAH group (p <0.01). The administration of CCL5 significantly increased CD45(+) glia and ICAM-1 level in the VPA treatment groups. CONCLUSION: VPA exerts its anti-vasospastic effect through the dual effect of inhibiting RANTES expression and reduced adhesion molecules. Besides, VPA also decreased CD45(+) cells transmigrated to the vascular wall. The administration of CCL5 significantly reversed the inhibitory effect of this compound on CD45(+) monocytes, E-selectin, and ICAM-1 level. This study also lends credence to support this compound could attenuate SAH induced adhesion molecules and neuro-inflammation in a CCL5 dependent mechanism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12950-015-0074-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4407545 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44075452015-04-24 Valproic acid attenuates intercellular adhesion molecule-1 and E-selectin through a chemokine ligand 5 dependent mechanism and subarachnoid hemorrhage induced vasospasm in a rat model Chang, Chih-Zen Wu, Shu-Chuan Lin, Chih-Lung Kwan, Aij-Lie J Inflamm (Lond) Research BACKGROUND: Up-regulation of regulated upon activation, normal T-cell expressed and secreted (RANTES/CCL5) and adhesion molecules is observed in the serum of animals following experimental subarachnoid hemorrhage (SAH). The present study was to examine the effect of valproic acid (VPA) on RANTES and alternation of adhesion molecules in this model. METHODS: A rodent SAH model was employed. Animals were randomly assigned into six groups. Basilar artery (BA) was harvested for intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule–1 (VCAM-1), and E-selectin evaluation (western blotting) and RANTES (rt-PCR). 1 ng CCL5 recombinant protein intrathecal injection was performed in the VPA + SAH groups. (N = 5). RESULTS: Convoluted internal elastic lamina, distorted endothelial wall, and smooth muscle micro-necrosis was prominently observed in the SAH groups, which is absent in the VPA treatment and the healthy controls. Treatment with VPA dose-dependently reduced the ICAM-1, E-selectin and RANTES level, compared with the SAH group (p <0.01). The administration of CCL5 significantly increased CD45(+) glia and ICAM-1 level in the VPA treatment groups. CONCLUSION: VPA exerts its anti-vasospastic effect through the dual effect of inhibiting RANTES expression and reduced adhesion molecules. Besides, VPA also decreased CD45(+) cells transmigrated to the vascular wall. The administration of CCL5 significantly reversed the inhibitory effect of this compound on CD45(+) monocytes, E-selectin, and ICAM-1 level. This study also lends credence to support this compound could attenuate SAH induced adhesion molecules and neuro-inflammation in a CCL5 dependent mechanism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12950-015-0074-3) contains supplementary material, which is available to authorized users. BioMed Central 2015-04-02 /pmc/articles/PMC4407545/ /pubmed/25908928 http://dx.doi.org/10.1186/s12950-015-0074-3 Text en © Chang et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Chang, Chih-Zen Wu, Shu-Chuan Lin, Chih-Lung Kwan, Aij-Lie Valproic acid attenuates intercellular adhesion molecule-1 and E-selectin through a chemokine ligand 5 dependent mechanism and subarachnoid hemorrhage induced vasospasm in a rat model |
title | Valproic acid attenuates intercellular adhesion molecule-1 and E-selectin through a chemokine ligand 5 dependent mechanism and subarachnoid hemorrhage induced vasospasm in a rat model |
title_full | Valproic acid attenuates intercellular adhesion molecule-1 and E-selectin through a chemokine ligand 5 dependent mechanism and subarachnoid hemorrhage induced vasospasm in a rat model |
title_fullStr | Valproic acid attenuates intercellular adhesion molecule-1 and E-selectin through a chemokine ligand 5 dependent mechanism and subarachnoid hemorrhage induced vasospasm in a rat model |
title_full_unstemmed | Valproic acid attenuates intercellular adhesion molecule-1 and E-selectin through a chemokine ligand 5 dependent mechanism and subarachnoid hemorrhage induced vasospasm in a rat model |
title_short | Valproic acid attenuates intercellular adhesion molecule-1 and E-selectin through a chemokine ligand 5 dependent mechanism and subarachnoid hemorrhage induced vasospasm in a rat model |
title_sort | valproic acid attenuates intercellular adhesion molecule-1 and e-selectin through a chemokine ligand 5 dependent mechanism and subarachnoid hemorrhage induced vasospasm in a rat model |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407545/ https://www.ncbi.nlm.nih.gov/pubmed/25908928 http://dx.doi.org/10.1186/s12950-015-0074-3 |
work_keys_str_mv | AT changchihzen valproicacidattenuatesintercellularadhesionmolecule1andeselectinthroughachemokineligand5dependentmechanismandsubarachnoidhemorrhageinducedvasospasminaratmodel AT wushuchuan valproicacidattenuatesintercellularadhesionmolecule1andeselectinthroughachemokineligand5dependentmechanismandsubarachnoidhemorrhageinducedvasospasminaratmodel AT linchihlung valproicacidattenuatesintercellularadhesionmolecule1andeselectinthroughachemokineligand5dependentmechanismandsubarachnoidhemorrhageinducedvasospasminaratmodel AT kwanaijlie valproicacidattenuatesintercellularadhesionmolecule1andeselectinthroughachemokineligand5dependentmechanismandsubarachnoidhemorrhageinducedvasospasminaratmodel |