title: The cross-talk between autophagy and endoplasmic reticulum stress in blood-spinal cord barrier disruption after spinal cord injury.
abstract: Spinal cord injury induces the disruption of blood-spinal cord barrier and triggers a complex array of tissue responses, including endoplasmic reticulum (ER) stress and autophagy. However, the roles of ER stress and autophagy in blood-spinal cord barrier disruption have not been discussed in acute spinal cord trauma. In the present study, we respectively detected the roles of ER stress and autophagy in blood-spinal cord barrier disruption after spinal cord injury. Besides, we also detected the cross-talking between autophagy and ER stress both in vivo and in vitro. ER stress inhibitor, 4-phenylbutyric acid, and autophagy inhibitor, chloroquine, were respectively or combinedly administrated in the model of acute spinal cord injury rats. At day 1 after spinal cord injury, blood-spinal cord barrier was disrupted and activation of ER stress and autophagy were involved in the rat model of trauma. Inhibition of ER stress by treating with 4-phenylbutyric acid decreased blood-spinal cord barrier permeability, prevented the loss of tight junction (TJ) proteins and reduced autophagy activation after spinal cord injury. On the contrary, inhibition of autophagy by treating with chloroquine exacerbated blood-spinal cord barrier permeability, promoted the loss of TJ proteins and enhanced ER stress after spinal cord injury. When 4-phenylbutyric acid and chloroquine were combinedly administrated in spinal cord injury rats, chloroquine abolished the blood-spinal cord barrier protective effect of 4-phenylbutyric acid by exacerbating ER stress after spinal cord injury, indicating that the cross-talking between autophagy and ER stress may play a central role on blood-spinal cord barrier integrity in acute spinal cord injury. The present study illustrates that ER stress induced by spinal cord injury plays a detrimental role on blood-spinal cord barrier integrity, on the contrary, autophagy induced by spinal cord injury plays a furthersome role in blood-spinal cord barrier integrity in acute spinal cord injury.
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 China.|Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: The Institute of Life Sciences, Wenzhou University, Wenzhou 325035, China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 China.
authors.forename: Yanlong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 China.|Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 China.
authors.forename: Zili
authors.initials: Z
authors.lastname: He
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zou
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 China.|Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 China.|Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 China.|Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 China.
authors.forename: Zengming
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 China.|Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Affiliated Cixi People's Hospital, Wenzhou Medical University, Ningbo, 315300, China.
authors.forename: Fenzan
authors.initials: F
authors.lastname: Wu
authors.affiliation: The Institute of Life Sciences, Wenzhou University, Wenzhou 325035, China.
authors.forename: Fanhua
authors.initials: F
authors.lastname: Gong
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 China.
authors.forename: Huazi
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 China.|Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D023421:Models, Animal; D010654:Phenylbutyrates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D062725:Tight Junction Proteins / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000502:physiology*
chemical_list: D010654:Phenylbutyrates; D062725:Tight Junction Proteins; C075773:4-phenylbutyric acid; D002738:Chloroquine
keywords: autophagy; blood-spinal cord barrier (BSCB); endoplasmic reticulum (ER) stress; spinal cord injury (SCI)