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Combined treatment of sodium ferulate, n‐butylidenephthalide, and ADSCs rehabilitates neurovascular unit in rats after photothrombotic stroke

The remodelling of structural and functional neurovascular unit (NVU) becomes a central therapeutic strategy after cerebral ischaemic stroke. In the present study, we investigated the effect of combined therapy of sodium ferulate (SF), n‐butylidenephthalide (BP) and adipose‐derived stromal cells (AD...

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Autores principales: Zhao, Yong‐Hua, Liu, Nai‐Wei, Ke, Chien‐Chih, Liu, Bo‐Wen, Chen, Yi‐An, Luo, Cheng, Zhang, Qian, Xia, Zhen‐Yan, Liu, Ren‐Shyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307846/
https://www.ncbi.nlm.nih.gov/pubmed/30421523
http://dx.doi.org/10.1111/jcmm.13894
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author Zhao, Yong‐Hua
Liu, Nai‐Wei
Ke, Chien‐Chih
Liu, Bo‐Wen
Chen, Yi‐An
Luo, Cheng
Zhang, Qian
Xia, Zhen‐Yan
Liu, Ren‐Shyan
author_facet Zhao, Yong‐Hua
Liu, Nai‐Wei
Ke, Chien‐Chih
Liu, Bo‐Wen
Chen, Yi‐An
Luo, Cheng
Zhang, Qian
Xia, Zhen‐Yan
Liu, Ren‐Shyan
author_sort Zhao, Yong‐Hua
collection PubMed
description The remodelling of structural and functional neurovascular unit (NVU) becomes a central therapeutic strategy after cerebral ischaemic stroke. In the present study, we investigated the effect of combined therapy of sodium ferulate (SF), n‐butylidenephthalide (BP) and adipose‐derived stromal cells (ADSCs) to ameliorate the injured NVU in the photochemically induced thrombotic stroke in rats. After solely or combined treatment, the neovascularization, activation of astrocytes, neurogenesis, expressions of vascular endothelial growth factor (VEGF) and claudin‐5 were assessed by immunohistochemical or immunofluorescence staining. In order to uncover the underlying mechanism of therapeutic effect, signalling of protein kinase B/mammalian target of rapamycin (AKT/mTOR), extracellular signal‐regulated kinase 1/2 (ERK1/2), and Notch1 in infarct zone were analysed by western blot. (18)F‐2‐deoxy‐glucose/positron emission tomography, magnetic resonance imaging, Evans blue staining were employed to evaluate the glucose metabolism, cerebral blood flow (CBF), and brain‐blood barrier (BBB) permeability, respectively. The results showed that combined treatment increased the neovascularization, neurogenesis, and VEGF secretion, modulated the astrocyte activation, enhanced the regional CBF, and glucose metabolism, as well as reduced BBB permeability and promoted claudin‐5 expression, indicating the restoration of structure and function of NVU. The activation of ERK1/2 and Notch1 pathways and inhibition of AKT/mTOR pathway might be involved in the therapeutic mechanism. In summary, we have demonstrated that combined ADSCs with SF and BP, targeting the NVU remodelling, is a potential treatment for ischaemic stroke. These results may provide valuable information for developing future combined cellular and pharmacological therapeutic strategy for ischaemic stroke.
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spelling pubmed-63078462019-01-04 Combined treatment of sodium ferulate, n‐butylidenephthalide, and ADSCs rehabilitates neurovascular unit in rats after photothrombotic stroke Zhao, Yong‐Hua Liu, Nai‐Wei Ke, Chien‐Chih Liu, Bo‐Wen Chen, Yi‐An Luo, Cheng Zhang, Qian Xia, Zhen‐Yan Liu, Ren‐Shyan J Cell Mol Med Original Articles The remodelling of structural and functional neurovascular unit (NVU) becomes a central therapeutic strategy after cerebral ischaemic stroke. In the present study, we investigated the effect of combined therapy of sodium ferulate (SF), n‐butylidenephthalide (BP) and adipose‐derived stromal cells (ADSCs) to ameliorate the injured NVU in the photochemically induced thrombotic stroke in rats. After solely or combined treatment, the neovascularization, activation of astrocytes, neurogenesis, expressions of vascular endothelial growth factor (VEGF) and claudin‐5 were assessed by immunohistochemical or immunofluorescence staining. In order to uncover the underlying mechanism of therapeutic effect, signalling of protein kinase B/mammalian target of rapamycin (AKT/mTOR), extracellular signal‐regulated kinase 1/2 (ERK1/2), and Notch1 in infarct zone were analysed by western blot. (18)F‐2‐deoxy‐glucose/positron emission tomography, magnetic resonance imaging, Evans blue staining were employed to evaluate the glucose metabolism, cerebral blood flow (CBF), and brain‐blood barrier (BBB) permeability, respectively. The results showed that combined treatment increased the neovascularization, neurogenesis, and VEGF secretion, modulated the astrocyte activation, enhanced the regional CBF, and glucose metabolism, as well as reduced BBB permeability and promoted claudin‐5 expression, indicating the restoration of structure and function of NVU. The activation of ERK1/2 and Notch1 pathways and inhibition of AKT/mTOR pathway might be involved in the therapeutic mechanism. In summary, we have demonstrated that combined ADSCs with SF and BP, targeting the NVU remodelling, is a potential treatment for ischaemic stroke. These results may provide valuable information for developing future combined cellular and pharmacological therapeutic strategy for ischaemic stroke. John Wiley and Sons Inc. 2018-11-12 2019-01 /pmc/articles/PMC6307846/ /pubmed/30421523 http://dx.doi.org/10.1111/jcmm.13894 Text en © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Zhao, Yong‐Hua
Liu, Nai‐Wei
Ke, Chien‐Chih
Liu, Bo‐Wen
Chen, Yi‐An
Luo, Cheng
Zhang, Qian
Xia, Zhen‐Yan
Liu, Ren‐Shyan
Combined treatment of sodium ferulate, n‐butylidenephthalide, and ADSCs rehabilitates neurovascular unit in rats after photothrombotic stroke
title Combined treatment of sodium ferulate, n‐butylidenephthalide, and ADSCs rehabilitates neurovascular unit in rats after photothrombotic stroke
title_full Combined treatment of sodium ferulate, n‐butylidenephthalide, and ADSCs rehabilitates neurovascular unit in rats after photothrombotic stroke
title_fullStr Combined treatment of sodium ferulate, n‐butylidenephthalide, and ADSCs rehabilitates neurovascular unit in rats after photothrombotic stroke
title_full_unstemmed Combined treatment of sodium ferulate, n‐butylidenephthalide, and ADSCs rehabilitates neurovascular unit in rats after photothrombotic stroke
title_short Combined treatment of sodium ferulate, n‐butylidenephthalide, and ADSCs rehabilitates neurovascular unit in rats after photothrombotic stroke
title_sort combined treatment of sodium ferulate, n‐butylidenephthalide, and adscs rehabilitates neurovascular unit in rats after photothrombotic stroke
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307846/
https://www.ncbi.nlm.nih.gov/pubmed/30421523
http://dx.doi.org/10.1111/jcmm.13894
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