title: Melatonin treatment protects against acute spinal cord injury-induced disruption of blood spinal cord barrier in mice.
abstract: The spinal cord microcirculation plays a critically important role in maintaining the normal function of spinal cord neurons, glial cells, and axons. Previous researches were largely focused on improved neurological manifestations of spinal cord injury (SCI) while ignoring to improve spinal cord microcirculation disorder after melatonin treatment. Therefore, the mechanism of melatonin that affects blood spinal cord barrier (BSCB) integrity and microcirculation in SCI remains unclear. The present study was performed to investigate the effect of melatonin on the BSCB in a SCI mice model. Melatonin (5, 10, 25, 50, 100 mg/kg i.p.) was administered to mice immediately following SCI. Compared to the 48 h post-SCI group, mice treated with melatonin (50 mg/kg) exhibited significantly reduced BSCB permeability. Additionally, melatonin treatment restrained microvessel loss; attenuated edema; protected the tight junction proteins, endothelial cells, and pericytes; decreased the number of cell apoptosis; and reduced MMP3/AQP4/HIF-1α/VEGF/VEGFR2 expression after SCI. Above all, our results clearly demonstrated that melatonin could stabilize microvascular barrier function and microcirculation of SCI, whose mechanism was to promote the repair of the damaged BSCB.
authors.affiliation: Key Laboratory for Microcirculation, Ministry of National Health of China, Institute of Microcirculation, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, 100005, Beijing, China.
authors.forename: Qingbin
authors.initials: Q
authors.lastname: Wu
authors.forename: Yingli
authors.initials: Y
authors.lastname: Jing
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Yuan
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.forename: Bingwei
authors.initials: B
authors.lastname: Li
authors.forename: Mingming
authors.initials: M
authors.lastname: Liu
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
authors.forename: Shuying
authors.initials: S
authors.lastname: Liu
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Xiu
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism; D002199:Capillary Permeability; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D062725:Tight Junction Proteins; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse; D008550:Melatonin