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Combined treatment of sodium ferulate, n-butylidenephthalide, and ADSCs rehabilitates neurovascular unit in rats after photothrombotic stroke
Zhao Y.-H.7; Liu N.-W.7; Ke C.-C.1; Liu B.-W.7; Chen Y.-A.2; Luo C.7; Zhang Q.4; Xia Z.-Y.7; Liu R.-S.1
2019
Source PublicationJournal of Cellular and Molecular Medicine
ISSN15821838
Volume23Issue:1Pages:126-142
Abstract

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. 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.

KeywordAdipose-derived Stromal Cells N-butylidenephthalide Neurovascular Unit Rehabilitation Sodium Ferulate
DOI10.1111/jcmm.13894
URLView the original
Indexed BySCI
Language英语
WOS Research AreaCell Biology ; Research & Experimental Medicine
WOS SubjectCell Biology ; Medicine, Research & Experimental
WOS IDWOS:000454423300012
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Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorZhao Y.-H.
Affiliation1.National Yang-Ming University Taiwan
2.National Comprehensive Mouse Phenotyping and Drug Testing Center
3.Cheng Hsin General Hospital
4.Shenzhen People's Hospital
5.Kaohsiung Medical University
6.Veterans General Hospital-Taipei
7.Macau University of Science and Technology
Recommended Citation
GB/T 7714
Zhao Y.-H.,Liu N.-W.,Ke C.-C.,et al. Combined treatment of sodium ferulate, n-butylidenephthalide, and ADSCs rehabilitates neurovascular unit in rats after photothrombotic stroke[J]. Journal of Cellular and Molecular Medicine,2019,23(1):126-142.
APA Zhao Y.-H..,Liu N.-W..,Ke C.-C..,Liu B.-W..,Chen Y.-A..,...&Liu R.-S..(2019).Combined treatment of sodium ferulate, n-butylidenephthalide, and ADSCs rehabilitates neurovascular unit in rats after photothrombotic stroke.Journal of Cellular and Molecular Medicine,23(1),126-142.
MLA Zhao Y.-H.,et al."Combined treatment of sodium ferulate, n-butylidenephthalide, and ADSCs rehabilitates neurovascular unit in rats after photothrombotic stroke".Journal of Cellular and Molecular Medicine 23.1(2019):126-142.
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