Role of Periostin in Early Brain Injury After Subarachnoid Hemorrhage in Mice

• Published in: Stroke (1970) 2017-04, Vol.48 (4), p.1108-1111
• Main Authors: Liu, Lei, Kawakita, Fumihiro, Fujimoto, Masashi, Nakano, Fumi, Imanaka-Yoshida, Kyoko, Yoshida, Toshimichi, Suzuki, Hidenori
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Blood-Brain Barrier - metabolism; Brain Injuries - metabolism; Cell Adhesion Molecules - immunology; Cell Adhesion Molecules - metabolism; Disease Models, Animal; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Recombinant Proteins; Subarachnoid Hemorrhage - complications; Subarachnoid Hemorrhage - metabolism; Tenascin - metabolism
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/STROKEAHA.117.016629

BACKGROUND AND PURPOSE—A matricellular protein tenascin-C is implicated in early brain injury after experimental subarachnoid hemorrhage (SAH). This study first evaluated the role of another matricellular protein periostin and the relationships with tenascin-C in post-SAH early brain injury. METHODS—Wild-type (n=226) and tenascin-C knockout (n=9) C57BL/6 male adult mice underwent sham or filament perforation SAH modeling. Vehicle, anti-periostin antibody, or recombinant periostin was randomly administrated by an intracerebroventricular injection at 30 minutes post-modeling. Neuroscores, SAH grading, brain water content, immunostaining, and Western blotting were blindly evaluated at 24 to 48 hours post-SAH. RESULTS—Periostin was induced in brain capillary endothelial cells and neurons at 24 hours post-SAH. Anti-periostin antibody improved post-SAH neurobehavior, brain edema, and blood–brain barrier disruption associated with downregulation of tenascin-C, inactivation of p38, extracellular signal-related kinase 1/2 and matrix metalloproteinase-9, and subsequent preservation of zona occludens-1. Recombinant periostin aggravated post-SAH brain edema and tenascin-C induction. Tenascin-C knockout prevented post-SAH neurobehavioral impairments and periostin induction. CONCLUSIONS—Periostin may cause post-SAH early brain injury through activating downstream signaling pathways and interacting with tenascin-C, providing a novel approach for the treatment of early brain injury.