title: Phenylbutyrate prevents disruption of blood-spinal cord barrier by inhibiting endoplasmic reticulum stress after spinal cord injury.
abstract: This study aims to investigate the role of endocytoplasmic reticulum (ER) stress induced by spinal cord injury (SCI) in blood-spinal cord barrier (BSCB) disruption and the effect of phenylbutyrate (PBA) on BSCB disruption after SCI. After a moderate contusion injury at the T9 level of spinal cord with a vascular clip, PBA was immediately administered into injured rat via intraperitoneal injection (100 mg/kg) and then further treated once a day for 2 weeks for behavior test. Spinal cord was collected at 1 day post-injury for evaluation of the effects of ER stress and PBA on BSCB disruption after SCI. PBA significantly attenuated BSCB permeability and degradation of tight junction molecules such as P120, β-catenin, Occludin and Claudin5 at 1 day after injury and improved functional recovery in the rat model of trauma. The BSCB protective effect of PBA is related to the inhibition of ER stress induced by SCI. In addition, PBA significantly inhibited the increase of ER stress markers and prevents loss of tight junction and adherens junction proteins in TG-treated human brain microvascular endothelial cells (HBMEC). Taken together, our data demonstrate that therapeutic strategies targeting ER stress may be suitable for the therapy of preserving BSCB integrity after SCI. PBA may be a new candidate as a therapeutic agent for protecting SCI by a compromised BSCB.
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical UniversityWenzhou, Zhejiang 325035, China; Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical UniversityWenzhou, Zhejiang 325035, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University Wenzhou, Zhejiang 325035, China.
authors.forename: Libing
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical UniversityWenzhou, Zhejiang 325035, China; Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical UniversityWenzhou, Zhejiang 325035, China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Zheng
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical UniversityWenzhou, Zhejiang 325035, China; Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical UniversityWenzhou, Zhejiang 325035, China.
authors.forename: Sipin
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University Wenzhou, Zhejiang 325035, China.
authors.forename: Hongxue
authors.initials: H
authors.lastname: Shi
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University Wenzhou, Zhejiang 325035, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University Wenzhou, Zhejiang 325035, China.
authors.forename: Zhouguang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Cixi People's Hospital, Wenzhou Medical University Ningbo 315300, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Emergency, The Second Affiliated Hospital Hospital, Wenzhou Medical University Wenzhou 325035, China.
authors.forename: Daqing
authors.initials: D
authors.lastname: Chen
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University Wenzhou, Zhejiang 325035, China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical University Wenzhou, Zhejiang 325035, China.
authors.forename: Huazi
authors.initials: H
authors.lastname: Xu
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University Wenzhou, Zhejiang 325035, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
keywords: Blood-spinal cord barrier; ER stress; phenylbutyrate; spinal cord injury