SPARC Aggravates Blood-Brain Barrier Disruption via Integrin V3/MAPKs/MMP-9 Signaling Pathway after Subarachnoid Hemorrhage

Authors

Takeshi Okada, Department of Neurosurgery, Kuwana City Medical Center, 3-11 Kotobuki-cho, Kuwana, Mie 511-0061, Japan.
Hidenori Suzuki, Department of Neurosurgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
Zachary D. Travis, Department of Physiology and Pharmacology, Loma Linda University, Risley Hall, Room 219, 11041 Campus St., Loma Linda, CA 92354, USA.Follow
Orhan Altay, Department of Physiology and Pharmacology, Loma Linda University, Risley Hall, Room 219, 11041 Campus St., Loma Linda, CA 92354, USA.
Jiping Tang, Department of Physiology and Pharmacology, Loma Linda University, Risley Hall, Room 219, 11041 Campus St., Loma Linda, CA 92354, USA.Follow
John H. Zhang, Department of Physiology and Pharmacology, Loma Linda University, Risley Hall, Room 219, 11041 Campus St., Loma Linda, CA 92354, USA.Follow

Document Type

Article

Publication Date

1-1-2021

Publication Title

Oxidative medicine and cellular longevity

E-ISSN

1942-0994

Abstract

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 V3 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 V3 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 V3 signaling pathway.

Volume

2021

First Page

9739977

DOI

10.1155/2021/9739977

PubMed ID

34804372

Recommended Citation

Okada, Takeshi; Suzuki, Hidenori; Travis, Zachary D.; Altay, Orhan; Tang, Jiping; and Zhang, John H., "SPARC Aggravates Blood-Brain Barrier Disruption via Integrin V3/MAPKs/MMP-9 Signaling Pathway after Subarachnoid Hemorrhage" (2021). Loma Linda University Faculty Publications. 295.
https://scholarsrepository.llu.edu/fac_pubs/295