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1, 25-D(3) Protects From Cerebral Ischemia by Maintaining BBB Permeability via PPAR-γ Activation
The blood-brain barrier (BBB) is a physical and biochemical barrier that maintains cerebral homeostasis. BBB dysfunction in an ischemic stroke, results in brain injury and subsequent neurological impairment. The aim of this study was to determine the possible protective effects of 1, 25-dihydroxyvit...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304345/ https://www.ncbi.nlm.nih.gov/pubmed/30618630 http://dx.doi.org/10.3389/fncel.2018.00480 |
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author | Guo, Ting Wang, Yanqiang Guo, Yuanfang Wu, Shuguang Chen, Weiwei Liu, Na Wang, Yu Geng, Deqin |
author_facet | Guo, Ting Wang, Yanqiang Guo, Yuanfang Wu, Shuguang Chen, Weiwei Liu, Na Wang, Yu Geng, Deqin |
author_sort | Guo, Ting |
collection | PubMed |
description | The blood-brain barrier (BBB) is a physical and biochemical barrier that maintains cerebral homeostasis. BBB dysfunction in an ischemic stroke, results in brain injury and subsequent neurological impairment. The aim of this study was to determine the possible protective effects of 1, 25-dihydroxyvitamin D(3) [1, 25(OH)(2)D(3), 1, 25-D(3), vit D] on BBB dysfunction, at the early stages of an acute ischemic brain injury. We analyzed the effects of 1, 25-D(3) on BBB integrity in terms of histopathological changes, the neurological deficit, infarct size and the expression of brain derived neurotrophic factor (BDNF), in a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model. BBB permeability and the expression of permeability-related proteins in the brain were also evaluated by Evans blue (EB) staining and Western blotting respectively. To determine the possible mechanism underlying the role of 1, 25-D(3) in BBB maintenance, after MCAO/R, the rats were treated with the specific peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor GW9662. Supplementation with 1, 25-D(3) markedly improved the neurological scores of the rats, decreased the infarct volume, prevented neuronal deformation and upregulated the expression of the tight junction (TJ) and BDNF proteins in their brains. Furthermore, it activated PPARγ but downregulated neuro-inflammatory cytokines such as nuclear factor kappa-B (NF-κB) and tumor necrosis factor-α (TNF-α), after MCAO/R. Taken together, 1, 25-D(3) protects against cerebral ischemia by maintaining BBB permeability, upregulating the level of BDNF and inhibiting PPARγ-mediated neuro-inflammation. |
format | Online Article Text |
id | pubmed-6304345 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63043452019-01-07 1, 25-D(3) Protects From Cerebral Ischemia by Maintaining BBB Permeability via PPAR-γ Activation Guo, Ting Wang, Yanqiang Guo, Yuanfang Wu, Shuguang Chen, Weiwei Liu, Na Wang, Yu Geng, Deqin Front Cell Neurosci Neuroscience The blood-brain barrier (BBB) is a physical and biochemical barrier that maintains cerebral homeostasis. BBB dysfunction in an ischemic stroke, results in brain injury and subsequent neurological impairment. The aim of this study was to determine the possible protective effects of 1, 25-dihydroxyvitamin D(3) [1, 25(OH)(2)D(3), 1, 25-D(3), vit D] on BBB dysfunction, at the early stages of an acute ischemic brain injury. We analyzed the effects of 1, 25-D(3) on BBB integrity in terms of histopathological changes, the neurological deficit, infarct size and the expression of brain derived neurotrophic factor (BDNF), in a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model. BBB permeability and the expression of permeability-related proteins in the brain were also evaluated by Evans blue (EB) staining and Western blotting respectively. To determine the possible mechanism underlying the role of 1, 25-D(3) in BBB maintenance, after MCAO/R, the rats were treated with the specific peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor GW9662. Supplementation with 1, 25-D(3) markedly improved the neurological scores of the rats, decreased the infarct volume, prevented neuronal deformation and upregulated the expression of the tight junction (TJ) and BDNF proteins in their brains. Furthermore, it activated PPARγ but downregulated neuro-inflammatory cytokines such as nuclear factor kappa-B (NF-κB) and tumor necrosis factor-α (TNF-α), after MCAO/R. Taken together, 1, 25-D(3) protects against cerebral ischemia by maintaining BBB permeability, upregulating the level of BDNF and inhibiting PPARγ-mediated neuro-inflammation. Frontiers Media S.A. 2018-12-17 /pmc/articles/PMC6304345/ /pubmed/30618630 http://dx.doi.org/10.3389/fncel.2018.00480 Text en Copyright © 2018 Guo, Wang, Guo, Wu, Chen, Liu, Wang and Geng. http://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 | Neuroscience Guo, Ting Wang, Yanqiang Guo, Yuanfang Wu, Shuguang Chen, Weiwei Liu, Na Wang, Yu Geng, Deqin 1, 25-D(3) Protects From Cerebral Ischemia by Maintaining BBB Permeability via PPAR-γ Activation |
title | 1, 25-D(3) Protects From Cerebral Ischemia by Maintaining BBB Permeability via PPAR-γ Activation |
title_full | 1, 25-D(3) Protects From Cerebral Ischemia by Maintaining BBB Permeability via PPAR-γ Activation |
title_fullStr | 1, 25-D(3) Protects From Cerebral Ischemia by Maintaining BBB Permeability via PPAR-γ Activation |
title_full_unstemmed | 1, 25-D(3) Protects From Cerebral Ischemia by Maintaining BBB Permeability via PPAR-γ Activation |
title_short | 1, 25-D(3) Protects From Cerebral Ischemia by Maintaining BBB Permeability via PPAR-γ Activation |
title_sort | 1, 25-d(3) protects from cerebral ischemia by maintaining bbb permeability via ppar-γ activation |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304345/ https://www.ncbi.nlm.nih.gov/pubmed/30618630 http://dx.doi.org/10.3389/fncel.2018.00480 |
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