title: Inhibiting endoplasmic reticulum stress by lithium chloride contributes to the integrity of blood-spinal cord barrier and functional recovery after spinal cord injury.
abstract: Endoplasmic reticulum (ER) stress play important roles in the spinal cord injury (SCI), which including blood-spinal cord barrier (BSCB) disruption. Lithium chloride (LiCl) is a clinical drug for bipolar mood disorders and contributes to neuroprotection. This study aims to investigate the effects of LiCl on BSCB disruption and the ER stress pathway induced by spinal cord injury. We examined the integrity of the BSCB with Evans Blue dye and macrophages extravasation, measured the microvessels loss, the junction proteins degeneration, the activation ER stress, and the locomotor function recovery. Our data indicated that LiCl treatment could attenuates BSCB disruption and improved the recovery of functional locomotion in rats SCI model, reduced the structure damage and number loss of microvessels, increased the expressions of junction proteins, including p120, β-catenin, occludin, and claudin-5, via reversed the upregulated ER stress associated proteins. In addition, LiCl significantly inhibited the increase of ER stress markers and prevents loss of junction proteins in thapsigargin (TG)-treated human brain microvascular endothelial cells (HBMEC). These findings suggest that LiCl treatment alleviates BSCB disruption and promote the neurological function recovery after SCI, partly through inhibiting the activation of ER stress.
authors.affiliation: Department of Orthopaedics, The Second Affliated Hospital and Yuying Children's Hospital, Wenzhou Medical UniversityWenzhou 325035, Zhejiang, China; Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical UniversityWenzhou 325035, Zhejiang, China.
authors.forename: Zili
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Orthopaedics, The Second Affliated Hospital and Yuying Children's Hospital, Wenzhou Medical University Wenzhou 325035, Zhejiang, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Orthopaedics, The Second Affliated Hospital and Yuying Children's Hospital, Wenzhou Medical UniversityWenzhou 325035, Zhejiang, China; Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical UniversityWenzhou 325035, Zhejiang, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, The Second Affliated Hospital and Yuying Children's Hospital, Wenzhou Medical UniversityWenzhou 325035, Zhejiang, China; Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical UniversityWenzhou 325035, Zhejiang, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, The Second Affliated Hospital and Yuying Children's Hospital, Wenzhou Medical University Wenzhou 325035, Zhejiang, China.
authors.forename: Zengming
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Orthopaedics, The Second Affliated Hospital and Yuying Children's Hospital, Wenzhou Medical University Wenzhou 325035, Zhejiang, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University Wenzhou 325035, Zhejiang, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University Wenzhou 325035, Zhejiang, China.
authors.forename: Zhouguang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, The Second Affliated Hospital and Yuying Children's Hospital, Wenzhou Medical University Wenzhou 325035, Zhejiang, China.
authors.forename: Huazi
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Orthopaedics, The Second Affliated Hospital and Yuying Children's Hospital, Wenzhou Medical UniversityWenzhou 325035, Zhejiang, China; Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical UniversityWenzhou 325035, Zhejiang, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
keywords: Blood-spinal cord barrier; endoplasmic reticulum stress; lithium chloride; spinal cord injury