SPARC Aggravates Blood-Brain Barrier Disruption via Integrin αVβ3/MAPKs/MMP-9 Signaling Pathway after Subarachnoid Hemorrhage

Blood-brain barrier (BBB) disruption is a common and critical pathology following subarachnoid hemorrhage (SAH). We investigated the BBB disruption property of secreted protein acidic and rich in cysteine (SPARC) after SAH. A total of 197 rats underwent endovascular perforation to induce SAH or sham...

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Autores principales:	Takeshi Okada, Hidenori Suzuki, Zachary D. Travis, Orhan Altay, Jiping Tang, John H. Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/bfa51321fecc4473ad2db28f7f5fa266
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spelling	oai:doaj.org-article:bfa51321fecc4473ad2db28f7f5fa2662021-11-22T01:10:54ZSPARC Aggravates Blood-Brain Barrier Disruption via Integrin αVβ3/MAPKs/MMP-9 Signaling Pathway after Subarachnoid Hemorrhage1942-099410.1155/2021/9739977https://doaj.org/article/bfa51321fecc4473ad2db28f7f5fa2662021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/9739977https://doaj.org/toc/1942-0994Blood-brain barrier (BBB) disruption is a common and critical pathology following subarachnoid hemorrhage (SAH). We investigated the BBB disruption property of secreted protein acidic and rich in cysteine (SPARC) after SAH. A total of 197 rats underwent endovascular perforation to induce SAH or sham operation. Small interfering ribonucleic acid (siRNA) for SPARC or scrambled siRNA was administered intracerebroventricularly to rats 48 h before SAH. Anti-SPARC monoclonal antibody (mAb) 236 for functional blocking or normal mouse immunoglobulin G (IgG) was administered intracerebroventricularly 1 h after SAH. Selective integrin αVβ3 inhibitor cyclo(-RGDfK) or phosphate-buffered saline was administered intranasally 1 h before SAH, along with recombinant SPARC treatment. Neurobehavior, SAH severity, brain edema, immunohistochemical staining, and Western blot were evaluated. The expression of SPARC and integrin αVβ3 was upregulated after SAH in the endothelial cells. SPARC siRNA and anti-SPARC mAb 236 prevented neuroimpairments and brain edema through protection of BBB as measured by IgG extravasation 24 and 72 h after SAH. Recombinant SPARC aggravated neuroimpairments and cyclo(-RGDfK) suppressed the harmful neurological effects via inhibition of activated c-Jun N-terminal kinase, p38, and matrix metalloproteinase-9 followed by retention of endothelial junction proteins. SPARC may induce post-SAH BBB disruption via integrin αVβ3 signaling pathway.Takeshi OkadaHidenori SuzukiZachary D. TravisOrhan AltayJiping TangJohn H. ZhangHindawi LimitedarticleCytologyQH573-671ENOxidative Medicine and Cellular Longevity, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Takeshi Okada Hidenori Suzuki Zachary D. Travis Orhan Altay Jiping Tang John H. Zhang SPARC Aggravates Blood-Brain Barrier Disruption via Integrin αVβ3/MAPKs/MMP-9 Signaling Pathway after Subarachnoid Hemorrhage
description	Blood-brain barrier (BBB) disruption is a common and critical pathology following subarachnoid hemorrhage (SAH). We investigated the BBB disruption property of secreted protein acidic and rich in cysteine (SPARC) after SAH. A total of 197 rats underwent endovascular perforation to induce SAH or sham operation. Small interfering ribonucleic acid (siRNA) for SPARC or scrambled siRNA was administered intracerebroventricularly to rats 48 h before SAH. Anti-SPARC monoclonal antibody (mAb) 236 for functional blocking or normal mouse immunoglobulin G (IgG) was administered intracerebroventricularly 1 h after SAH. Selective integrin αVβ3 inhibitor cyclo(-RGDfK) or phosphate-buffered saline was administered intranasally 1 h before SAH, along with recombinant SPARC treatment. Neurobehavior, SAH severity, brain edema, immunohistochemical staining, and Western blot were evaluated. The expression of SPARC and integrin αVβ3 was upregulated after SAH in the endothelial cells. SPARC siRNA and anti-SPARC mAb 236 prevented neuroimpairments and brain edema through protection of BBB as measured by IgG extravasation 24 and 72 h after SAH. Recombinant SPARC aggravated neuroimpairments and cyclo(-RGDfK) suppressed the harmful neurological effects via inhibition of activated c-Jun N-terminal kinase, p38, and matrix metalloproteinase-9 followed by retention of endothelial junction proteins. SPARC may induce post-SAH BBB disruption via integrin αVβ3 signaling pathway.
format	article
author	Takeshi Okada Hidenori Suzuki Zachary D. Travis Orhan Altay Jiping Tang John H. Zhang
author_facet	Takeshi Okada Hidenori Suzuki Zachary D. Travis Orhan Altay Jiping Tang John H. Zhang
author_sort	Takeshi Okada
title	SPARC Aggravates Blood-Brain Barrier Disruption via Integrin αVβ3/MAPKs/MMP-9 Signaling Pathway after Subarachnoid Hemorrhage
title_short	SPARC Aggravates Blood-Brain Barrier Disruption via Integrin αVβ3/MAPKs/MMP-9 Signaling Pathway after Subarachnoid Hemorrhage
title_full	SPARC Aggravates Blood-Brain Barrier Disruption via Integrin αVβ3/MAPKs/MMP-9 Signaling Pathway after Subarachnoid Hemorrhage
title_fullStr	SPARC Aggravates Blood-Brain Barrier Disruption via Integrin αVβ3/MAPKs/MMP-9 Signaling Pathway after Subarachnoid Hemorrhage
title_full_unstemmed	SPARC Aggravates Blood-Brain Barrier Disruption via Integrin αVβ3/MAPKs/MMP-9 Signaling Pathway after Subarachnoid Hemorrhage
title_sort	sparc aggravates blood-brain barrier disruption via integrin αvβ3/mapks/mmp-9 signaling pathway after subarachnoid hemorrhage
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/bfa51321fecc4473ad2db28f7f5fa266
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SPARC Aggravates Blood-Brain Barrier Disruption via Integrin αVβ3/MAPKs/MMP-9 Signaling Pathway after Subarachnoid Hemorrhage

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