Semaphorin3A elevates vascular permeability and contributes to cerebral ischemia-induced brain damage

Semaphorin 3A (Sema3A) increased significantly in mouse brain following cerebral ischemia. However, the role of Sema3A in stroke brain remains unknown. Our aim was to determine wether Sema3A functions as a vascular permeability factor and contributes to ischemic brain damage. Recombinant Sema3A inje...

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Main Authors:	Hou, Sheng Tao, Nilchi, Ladan, Li, Xuesheng, Gangaraju, Sandhya, Jiang, Susan X., Aylsworth, Amy, Monette, Robert, Slinn, Jacqueline
Format:	Online
Language:	English
Published:	Nature Publishing Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4298747/

id	pubmed-4298747
recordtype	oai_dc
spelling	pubmed-42987472015-02-03 Semaphorin3A elevates vascular permeability and contributes to cerebral ischemia-induced brain damage Hou, Sheng Tao Nilchi, Ladan Li, Xuesheng Gangaraju, Sandhya Jiang, Susan X. Aylsworth, Amy Monette, Robert Slinn, Jacqueline Article Semaphorin 3A (Sema3A) increased significantly in mouse brain following cerebral ischemia. However, the role of Sema3A in stroke brain remains unknown. Our aim was to determine wether Sema3A functions as a vascular permeability factor and contributes to ischemic brain damage. Recombinant Sema3A injected intradermally to mouse skin, or stereotactically into the cerebral cortex, caused dose- and time-dependent increases in vascular permeability, with a degree comparable to that caused by injection of a known vascular permeability factor vascular endothelial growth factor receptors (VEGF). Application of Sema3A to cultured endothelial cells caused disorganization of F-actin stress fibre bundles and increased endothelial monolayer permeability, confirming Sema3A as a permeability factor. Sema3A-mediated F-actin changes in endothelial cells were through binding to the neuropilin2/VEGFR1 receptor complex, which in turn directly activates Mical2, a F-actin modulator. Down-regulation of Mical2, using specific siRNA, alleviated Sema3A-induced F-actin disorganization, cellular morphology changes and endothelial permeability. Importantly, ablation of Sema3A expression, cerebrovascular permeability and brain damage were significantly reduced in response to transient middle cerebral artery occlusion (tMCAO) and in a mouse model of cerebral ischemia/haemorrhagic transformation. Together, these studies demonstrated that Sema3A is a key mediator of cerebrovascular permeability and contributes to brain damage caused by cerebral ischemia. Nature Publishing Group 2015-01-20 /pmc/articles/PMC4298747/ /pubmed/25601765 http://dx.doi.org/10.1038/srep07890 Text en Copyright © 2015, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Hou, Sheng Tao Nilchi, Ladan Li, Xuesheng Gangaraju, Sandhya Jiang, Susan X. Aylsworth, Amy Monette, Robert Slinn, Jacqueline
spellingShingle	Hou, Sheng Tao Nilchi, Ladan Li, Xuesheng Gangaraju, Sandhya Jiang, Susan X. Aylsworth, Amy Monette, Robert Slinn, Jacqueline Semaphorin3A elevates vascular permeability and contributes to cerebral ischemia-induced brain damage
author_facet	Hou, Sheng Tao Nilchi, Ladan Li, Xuesheng Gangaraju, Sandhya Jiang, Susan X. Aylsworth, Amy Monette, Robert Slinn, Jacqueline
author_sort	Hou, Sheng Tao
title	Semaphorin3A elevates vascular permeability and contributes to cerebral ischemia-induced brain damage
title_short	Semaphorin3A elevates vascular permeability and contributes to cerebral ischemia-induced brain damage
title_full	Semaphorin3A elevates vascular permeability and contributes to cerebral ischemia-induced brain damage
title_fullStr	Semaphorin3A elevates vascular permeability and contributes to cerebral ischemia-induced brain damage
title_full_unstemmed	Semaphorin3A elevates vascular permeability and contributes to cerebral ischemia-induced brain damage
title_sort	semaphorin3a elevates vascular permeability and contributes to cerebral ischemia-induced brain damage
description	Semaphorin 3A (Sema3A) increased significantly in mouse brain following cerebral ischemia. However, the role of Sema3A in stroke brain remains unknown. Our aim was to determine wether Sema3A functions as a vascular permeability factor and contributes to ischemic brain damage. Recombinant Sema3A injected intradermally to mouse skin, or stereotactically into the cerebral cortex, caused dose- and time-dependent increases in vascular permeability, with a degree comparable to that caused by injection of a known vascular permeability factor vascular endothelial growth factor receptors (VEGF). Application of Sema3A to cultured endothelial cells caused disorganization of F-actin stress fibre bundles and increased endothelial monolayer permeability, confirming Sema3A as a permeability factor. Sema3A-mediated F-actin changes in endothelial cells were through binding to the neuropilin2/VEGFR1 receptor complex, which in turn directly activates Mical2, a F-actin modulator. Down-regulation of Mical2, using specific siRNA, alleviated Sema3A-induced F-actin disorganization, cellular morphology changes and endothelial permeability. Importantly, ablation of Sema3A expression, cerebrovascular permeability and brain damage were significantly reduced in response to transient middle cerebral artery occlusion (tMCAO) and in a mouse model of cerebral ischemia/haemorrhagic transformation. Together, these studies demonstrated that Sema3A is a key mediator of cerebrovascular permeability and contributes to brain damage caused by cerebral ischemia.
publisher	Nature Publishing Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4298747/
_version_	1613178080507985920

Semaphorin3A elevates vascular permeability and contributes to cerebral ischemia-induced brain damage

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