Lei Liu1, Fumihiro Kawakita1, Masashi Fujimoto1, Fumi Nakano1, Kyoko Imanaka-Yoshida1, Toshimichi Yoshida1, Hidenori Suzuki2. 1. From the Department of Neurosurgery (L.L., F.K., M.F., F.N., H.S.), Department of Pathology and Matrix Biology (K.I.-Y., T.Y.), and Research Center for Matrix Biology (K.I.-Y., T.Y., H.S.), Mie University Graduate School of Medicine, Tsu, Japan. 2. From the Department of Neurosurgery (L.L., F.K., M.F., F.N., H.S.), Department of Pathology and Matrix Biology (K.I.-Y., T.Y.), and Research Center for Matrix Biology (K.I.-Y., T.Y., H.S.), Mie University Graduate School of Medicine, Tsu, Japan. suzuki02@clin.medic.mie-u.ac.jp.
Abstract
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.
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.
Authors: Denise E Allard; Yan Wang; Jian Joel Li; Bridget Conley; Erin W Xu; David Sailer; Caellaigh Kimpston; Rebecca Notini; Collin-Jamal Smith; Emel Koseoglu; Joshua Starmer; Xiaopei L Zeng; James F Howard; Ahmet Hoke; Steven S Scherer; Maureen A Su Journal: J Clin Invest Date: 2018-09-17 Impact factor: 14.808