title: Retinoic Acid Prevents Disruption of Blood-Spinal Cord Barrier by Inducing Autophagic Flux After Spinal Cord Injury.
abstract: Spinal cord injury (SCI) induces the disruption of the blood-spinal cord barrier (BSCB), which leads to infiltration of blood cells, inflammatory responses and neuronal cell death, with subsequent development of spinal cord secondary damage. Recent reports pointed to an important role of retinoic acid (RA), the active metabolite of the vitamin A, in the induction of the blood-brain barrier (BBB) during human and mouse development, however, it is unknown whether RA plays a role in maintaining BSCB integrity under the pathological conditions such as SCI. In this study, we investigated the BSCB protective role of RA both in vivo and in vitro and demonstrated that autophagy are involved in the BSCB protective effect of RA. Our data show that RA attenuated BSCB permeability and also attenuated the loss of tight junction molecules such as P120, β-catenin, Occludin and Claudin5 after injury in vivo as well as in brain microvascular endothelial cells. In addition, RA administration improved functional recovery of the rat model of trauma. We also found that RA could significantly increase the expression of LC3-II and decrease the expression of p62 both in vivo and in vitro. Furthermore, combining RA with the autophagy inhibitor chloroquine (CQ) partially abolished its protective effect on the BSCB and exacerbated the loss of tight junctions. Together, our studies indicate that RA improved functional recovery in part by the prevention of BSCB disruption via the activation of autophagic flux after SCI.
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000, China.|School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000, China.|School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Zheng
authors.affiliation: School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Libing
authors.initials: L
authors.lastname: Ye
authors.affiliation: School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000, China.|School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Sipin
authors.initials: S
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Zheng
authors.affiliation: School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Qinghai
authors.initials: Q
authors.lastname: Xia
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000, China.|School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Zili
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000, China.|School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035, China. xfxj2000@126.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000, China. wzmcxu@163.com.
authors.forename: Huazi
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D001343:Autophagy; D001921:Brain / Q000098:blood supply; D051177:Catenins / Q000378:metabolism; D002478:Cells, Cultured; D057167:Claudins / Q000378:metabolism; D005260:Female; D006801:Humans; D055806:Microvessels / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D062793:Occludin / Q000378:metabolism; D010539:Permeability; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014212:Tretinoin / Q000494:pharmacology*; D051176:beta Catenin / Q000378:metabolism; D000095002:Delta Catenin
chemical_list: D051177:Catenins; D057167:Claudins; D062793:Occludin; D051176:beta Catenin; D014212:Tretinoin; D000095002:Delta Catenin
keywords: Autophagy; Blood-spinal cord barrier (BSCB); Retinoic acid (RA); Spinal cord injury (SCI)