BMSCs Regulate Astrocytes through TSG-6 to Protect the Blood-Brain Barrier after Subarachnoid Hemorrhage

Background. In patients with subarachnoid hemorrhage (SAH), the damage of the blood-brain barrier (BBB) can be life-threatening. Mesenchymal stem cells are widely used in clinical research due to their pleiotropic properties. This study is aimed at exploring the effect of BMSCs regulating astrocytes...

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Main Authors: Yilv Wan, Min Song, Xun Xie, Zhen Chen, Ziyun Gao, Xiang Wu, Rui Huang, Min Chen
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2021/5522291
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author Yilv Wan
Min Song
Xun Xie
Zhen Chen
Ziyun Gao
Xiang Wu
Rui Huang
Min Chen
author_facet Yilv Wan
Min Song
Xun Xie
Zhen Chen
Ziyun Gao
Xiang Wu
Rui Huang
Min Chen
author_sort Yilv Wan
collection DOAJ
description Background. In patients with subarachnoid hemorrhage (SAH), the damage of the blood-brain barrier (BBB) can be life-threatening. Mesenchymal stem cells are widely used in clinical research due to their pleiotropic properties. This study is aimed at exploring the effect of BMSCs regulating astrocytes on the BBB after SAH. Methods. The SAH model was established by perforating the blood vessels. BMSCs were transfected with TSG-6 inhibitor plasmid and cocultured with astrocytes. Intravenous transplantation of BMSCs was utilized to treat SAH rats. We performed ELISA, neurological scoring, Evans blue staining, NO measurement, immunofluorescence, BBB permeability, Western blot, HE staining, Nissl staining, and immunohistochemistry to evaluate the effect of BMSCs on astrocytes and BBB. Results. SAH rats showed BBB injury, increased BBB permeability, and brain histological damage. BMSCs will secrete TSG-6 after being activated by TNF-α. Under the influence of TSG-6, the NF-κB and MAPK signaling pathways of astrocytes were inhibited. The expression of iNOS was reduced, while occludin, claudin 3, and ZO-1 expression was increased. The production of harmful substances NO and ONOO- decreased. The level of inflammatory factors decreased. The apoptosis of astrocytes was weakened. TSG-6 secreted by BMSCs can relieve inflammation caused by SAH injury. The increase in BBB permeability of SAH rats was further reduced and the risk of rebleeding was reduced. Conclusion. BMSCs can regulate the activation of astrocytes through secreting TSG-6 in vivo and in vitro to protect BBB.
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spelling doaj-art-18394a8f05c948789764de87e9edca182025-02-03T07:24:01ZengWileyMediators of Inflammation0962-93511466-18612021-01-01202110.1155/2021/55222915522291BMSCs Regulate Astrocytes through TSG-6 to Protect the Blood-Brain Barrier after Subarachnoid HemorrhageYilv Wan0Min Song1Xun Xie2Zhen Chen3Ziyun Gao4Xiang Wu5Rui Huang6Min Chen7Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, ChinaThe Second Clinical Medical College of Nanchang University, Nanchang, Jiangxi 330000, ChinaThe Second Clinical Medical College of Nanchang University, Nanchang, Jiangxi 330000, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, ChinaBackground. In patients with subarachnoid hemorrhage (SAH), the damage of the blood-brain barrier (BBB) can be life-threatening. Mesenchymal stem cells are widely used in clinical research due to their pleiotropic properties. This study is aimed at exploring the effect of BMSCs regulating astrocytes on the BBB after SAH. Methods. The SAH model was established by perforating the blood vessels. BMSCs were transfected with TSG-6 inhibitor plasmid and cocultured with astrocytes. Intravenous transplantation of BMSCs was utilized to treat SAH rats. We performed ELISA, neurological scoring, Evans blue staining, NO measurement, immunofluorescence, BBB permeability, Western blot, HE staining, Nissl staining, and immunohistochemistry to evaluate the effect of BMSCs on astrocytes and BBB. Results. SAH rats showed BBB injury, increased BBB permeability, and brain histological damage. BMSCs will secrete TSG-6 after being activated by TNF-α. Under the influence of TSG-6, the NF-κB and MAPK signaling pathways of astrocytes were inhibited. The expression of iNOS was reduced, while occludin, claudin 3, and ZO-1 expression was increased. The production of harmful substances NO and ONOO- decreased. The level of inflammatory factors decreased. The apoptosis of astrocytes was weakened. TSG-6 secreted by BMSCs can relieve inflammation caused by SAH injury. The increase in BBB permeability of SAH rats was further reduced and the risk of rebleeding was reduced. Conclusion. BMSCs can regulate the activation of astrocytes through secreting TSG-6 in vivo and in vitro to protect BBB.http://dx.doi.org/10.1155/2021/5522291
spellingShingle Yilv Wan
Min Song
Xun Xie
Zhen Chen
Ziyun Gao
Xiang Wu
Rui Huang
Min Chen
BMSCs Regulate Astrocytes through TSG-6 to Protect the Blood-Brain Barrier after Subarachnoid Hemorrhage
Mediators of Inflammation
title BMSCs Regulate Astrocytes through TSG-6 to Protect the Blood-Brain Barrier after Subarachnoid Hemorrhage
title_full BMSCs Regulate Astrocytes through TSG-6 to Protect the Blood-Brain Barrier after Subarachnoid Hemorrhage
title_fullStr BMSCs Regulate Astrocytes through TSG-6 to Protect the Blood-Brain Barrier after Subarachnoid Hemorrhage
title_full_unstemmed BMSCs Regulate Astrocytes through TSG-6 to Protect the Blood-Brain Barrier after Subarachnoid Hemorrhage
title_short BMSCs Regulate Astrocytes through TSG-6 to Protect the Blood-Brain Barrier after Subarachnoid Hemorrhage
title_sort bmscs regulate astrocytes through tsg 6 to protect the blood brain barrier after subarachnoid hemorrhage
url http://dx.doi.org/10.1155/2021/5522291
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