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FTY720 Reduces Endothelial Cell Apoptosis and Remodels Neurovascular Unit after Experimental Traumatic Brain Injury

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. A sequence of pathological processes occurred when there is TBI. Previous studies showed that sphingosine-1-phosphate receptor 1 (S1PR1) played a critical role in inflammatory response in the brain after TBI. Thus, the...

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Autores principales: Cheng, Hao, Di, Guangfu, Gao, Chao-Chao, He, Guoyuan, Wang, Xue, Han, Yan-Ling, Sun, Le-an, Zhou, Meng-Liang, Jiang, Xiaochun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757143/
https://www.ncbi.nlm.nih.gov/pubmed/33390799
http://dx.doi.org/10.7150/ijms.49066
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author Cheng, Hao
Di, Guangfu
Gao, Chao-Chao
He, Guoyuan
Wang, Xue
Han, Yan-Ling
Sun, Le-an
Zhou, Meng-Liang
Jiang, Xiaochun
author_facet Cheng, Hao
Di, Guangfu
Gao, Chao-Chao
He, Guoyuan
Wang, Xue
Han, Yan-Ling
Sun, Le-an
Zhou, Meng-Liang
Jiang, Xiaochun
author_sort Cheng, Hao
collection PubMed
description Traumatic brain injury (TBI) is a major cause of death and disability worldwide. A sequence of pathological processes occurred when there is TBI. Previous studies showed that sphingosine-1-phosphate receptor 1 (S1PR1) played a critical role in inflammatory response in the brain after TBI. Thus, the present study was designed to evaluate the effects of the S1PR1 modulator FTY720 on neurovascular unit (NVU) after experimental TBI in mice. The weight-drop TBI method was used to induce TBI. Western blot (WB) was performed to determine the levels of SIPR1, claudin-5 and occludin at different time points. FTY720 was intraperitoneally administered to mice after TBI was induced. The terminal deoxynucleotidyl transferase-dUTP nick end labeling (TUNEL) assay was used to assess endothelial cell apoptosis. Immunofluorescence and WB were performed to measure the expression of tight junction proteins: claudin-5 and occludin. Evans blue (EB) permeability assay and brain water content were applied to evaluate the blood-brain barrier (BBB) permeability and brain edema. Immunohistochemistry was performed to assess the activation of astrocytes and microglia. The results showed that FTY720 administration reduced endothelial cell apoptosis and improved BBB permeability. FTY720 also attenuated astrocytes and microglia activation. Furthermore, treatment with FTY720 not only improved neurological function, but also increased the survival rate of mice significantly. These findings suggest that FTY720 administration restored the structure of the NVU after experimental TBI by decreasing endothelial cell apoptosis and attenuating the activation of astrocytes. Moreover, FTY720 might reduce inflammation in the brain by reducing the activation of microglia in TBI mice.
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spelling pubmed-77571432021-01-01 FTY720 Reduces Endothelial Cell Apoptosis and Remodels Neurovascular Unit after Experimental Traumatic Brain Injury Cheng, Hao Di, Guangfu Gao, Chao-Chao He, Guoyuan Wang, Xue Han, Yan-Ling Sun, Le-an Zhou, Meng-Liang Jiang, Xiaochun Int J Med Sci Research Paper Traumatic brain injury (TBI) is a major cause of death and disability worldwide. A sequence of pathological processes occurred when there is TBI. Previous studies showed that sphingosine-1-phosphate receptor 1 (S1PR1) played a critical role in inflammatory response in the brain after TBI. Thus, the present study was designed to evaluate the effects of the S1PR1 modulator FTY720 on neurovascular unit (NVU) after experimental TBI in mice. The weight-drop TBI method was used to induce TBI. Western blot (WB) was performed to determine the levels of SIPR1, claudin-5 and occludin at different time points. FTY720 was intraperitoneally administered to mice after TBI was induced. The terminal deoxynucleotidyl transferase-dUTP nick end labeling (TUNEL) assay was used to assess endothelial cell apoptosis. Immunofluorescence and WB were performed to measure the expression of tight junction proteins: claudin-5 and occludin. Evans blue (EB) permeability assay and brain water content were applied to evaluate the blood-brain barrier (BBB) permeability and brain edema. Immunohistochemistry was performed to assess the activation of astrocytes and microglia. The results showed that FTY720 administration reduced endothelial cell apoptosis and improved BBB permeability. FTY720 also attenuated astrocytes and microglia activation. Furthermore, treatment with FTY720 not only improved neurological function, but also increased the survival rate of mice significantly. These findings suggest that FTY720 administration restored the structure of the NVU after experimental TBI by decreasing endothelial cell apoptosis and attenuating the activation of astrocytes. Moreover, FTY720 might reduce inflammation in the brain by reducing the activation of microglia in TBI mice. Ivyspring International Publisher 2021-01-01 /pmc/articles/PMC7757143/ /pubmed/33390799 http://dx.doi.org/10.7150/ijms.49066 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Cheng, Hao
Di, Guangfu
Gao, Chao-Chao
He, Guoyuan
Wang, Xue
Han, Yan-Ling
Sun, Le-an
Zhou, Meng-Liang
Jiang, Xiaochun
FTY720 Reduces Endothelial Cell Apoptosis and Remodels Neurovascular Unit after Experimental Traumatic Brain Injury
title FTY720 Reduces Endothelial Cell Apoptosis and Remodels Neurovascular Unit after Experimental Traumatic Brain Injury
title_full FTY720 Reduces Endothelial Cell Apoptosis and Remodels Neurovascular Unit after Experimental Traumatic Brain Injury
title_fullStr FTY720 Reduces Endothelial Cell Apoptosis and Remodels Neurovascular Unit after Experimental Traumatic Brain Injury
title_full_unstemmed FTY720 Reduces Endothelial Cell Apoptosis and Remodels Neurovascular Unit after Experimental Traumatic Brain Injury
title_short FTY720 Reduces Endothelial Cell Apoptosis and Remodels Neurovascular Unit after Experimental Traumatic Brain Injury
title_sort fty720 reduces endothelial cell apoptosis and remodels neurovascular unit after experimental traumatic brain injury
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757143/
https://www.ncbi.nlm.nih.gov/pubmed/33390799
http://dx.doi.org/10.7150/ijms.49066
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