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Extracellular vesicle-mediated transfer of miR-21-5p from mesenchymal stromal cells to neurons alleviates early brain injury to improve cognitive function via the PTEN/Akt pathway after subarachnoid hemorrhage

Patients with subarachnoid hemorrhage (SAH) often suffer from cognitive function impairments even when they have received proper treatment, such as the clipping or coiling of aneurysms, and this causes problems with returning to work and burdens the family. Increasing attention has been paid to mese...

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Autores principales: Gao, Xiao, Xiong, Ye, Li, Qizhao, Han, Min, Shan, Dezhi, Yang, Guozheng, Zhang, Shouji, Xin, Danqing, Zhao, Rongrong, Wang, Zhen, Xue, Hao, Li, Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220929/
https://www.ncbi.nlm.nih.gov/pubmed/32404916
http://dx.doi.org/10.1038/s41419-020-2530-0
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author Gao, Xiao
Xiong, Ye
Li, Qizhao
Han, Min
Shan, Dezhi
Yang, Guozheng
Zhang, Shouji
Xin, Danqing
Zhao, Rongrong
Wang, Zhen
Xue, Hao
Li, Gang
author_facet Gao, Xiao
Xiong, Ye
Li, Qizhao
Han, Min
Shan, Dezhi
Yang, Guozheng
Zhang, Shouji
Xin, Danqing
Zhao, Rongrong
Wang, Zhen
Xue, Hao
Li, Gang
author_sort Gao, Xiao
collection PubMed
description Patients with subarachnoid hemorrhage (SAH) often suffer from cognitive function impairments even when they have received proper treatment, such as the clipping or coiling of aneurysms, and this causes problems with returning to work and burdens the family. Increasing attention has been paid to mesenchymal stem cell (MSC)-derived extracellular vesicle (MSC-EV) as promising therapeutic vesicles for stroke management. In this study, we explored the potential role of MSC-EV in a rat model of SAH. We observed that MSC-EV ameliorated early brain injury (EBI) after SAH by reducing the apoptosis of neurons and that SAH induced an increase in the expression level of miR-21 in the prefrontal cortex and hippocampus. In addition, using miRNA profiling and CSF sequencing data from the exRNA Atlas, we demonstrated that EV-derived miR-21 protected neurons from apoptosis and alleviated SAH-induced cognitive dysfunction. The neuroprotective role of MSC-EV was abrogated by miR-21 knockdown or the administration of MK2206, a PTEN/Akt inhibitor. Overall, our results suggest that MSC-EV promotes neuronal survival and alleviates EBI after SAH through transferring miR-21 to recipient neurons.
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spelling pubmed-72209292020-05-15 Extracellular vesicle-mediated transfer of miR-21-5p from mesenchymal stromal cells to neurons alleviates early brain injury to improve cognitive function via the PTEN/Akt pathway after subarachnoid hemorrhage Gao, Xiao Xiong, Ye Li, Qizhao Han, Min Shan, Dezhi Yang, Guozheng Zhang, Shouji Xin, Danqing Zhao, Rongrong Wang, Zhen Xue, Hao Li, Gang Cell Death Dis Article Patients with subarachnoid hemorrhage (SAH) often suffer from cognitive function impairments even when they have received proper treatment, such as the clipping or coiling of aneurysms, and this causes problems with returning to work and burdens the family. Increasing attention has been paid to mesenchymal stem cell (MSC)-derived extracellular vesicle (MSC-EV) as promising therapeutic vesicles for stroke management. In this study, we explored the potential role of MSC-EV in a rat model of SAH. We observed that MSC-EV ameliorated early brain injury (EBI) after SAH by reducing the apoptosis of neurons and that SAH induced an increase in the expression level of miR-21 in the prefrontal cortex and hippocampus. In addition, using miRNA profiling and CSF sequencing data from the exRNA Atlas, we demonstrated that EV-derived miR-21 protected neurons from apoptosis and alleviated SAH-induced cognitive dysfunction. The neuroprotective role of MSC-EV was abrogated by miR-21 knockdown or the administration of MK2206, a PTEN/Akt inhibitor. Overall, our results suggest that MSC-EV promotes neuronal survival and alleviates EBI after SAH through transferring miR-21 to recipient neurons. Nature Publishing Group UK 2020-05-13 /pmc/articles/PMC7220929/ /pubmed/32404916 http://dx.doi.org/10.1038/s41419-020-2530-0 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Gao, Xiao
Xiong, Ye
Li, Qizhao
Han, Min
Shan, Dezhi
Yang, Guozheng
Zhang, Shouji
Xin, Danqing
Zhao, Rongrong
Wang, Zhen
Xue, Hao
Li, Gang
Extracellular vesicle-mediated transfer of miR-21-5p from mesenchymal stromal cells to neurons alleviates early brain injury to improve cognitive function via the PTEN/Akt pathway after subarachnoid hemorrhage
title Extracellular vesicle-mediated transfer of miR-21-5p from mesenchymal stromal cells to neurons alleviates early brain injury to improve cognitive function via the PTEN/Akt pathway after subarachnoid hemorrhage
title_full Extracellular vesicle-mediated transfer of miR-21-5p from mesenchymal stromal cells to neurons alleviates early brain injury to improve cognitive function via the PTEN/Akt pathway after subarachnoid hemorrhage
title_fullStr Extracellular vesicle-mediated transfer of miR-21-5p from mesenchymal stromal cells to neurons alleviates early brain injury to improve cognitive function via the PTEN/Akt pathway after subarachnoid hemorrhage
title_full_unstemmed Extracellular vesicle-mediated transfer of miR-21-5p from mesenchymal stromal cells to neurons alleviates early brain injury to improve cognitive function via the PTEN/Akt pathway after subarachnoid hemorrhage
title_short Extracellular vesicle-mediated transfer of miR-21-5p from mesenchymal stromal cells to neurons alleviates early brain injury to improve cognitive function via the PTEN/Akt pathway after subarachnoid hemorrhage
title_sort extracellular vesicle-mediated transfer of mir-21-5p from mesenchymal stromal cells to neurons alleviates early brain injury to improve cognitive function via the pten/akt pathway after subarachnoid hemorrhage
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220929/
https://www.ncbi.nlm.nih.gov/pubmed/32404916
http://dx.doi.org/10.1038/s41419-020-2530-0
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