Microvascular protective role of pericytes in melatonin-treated spinal cord injury in the C57BL/6 mice

Background Pericytes,located on microvessels,help to maintain vascular stability and blood-brain barrier integrity.The influence of pericytes on microvessels after spinal cord injury (SCI) is less clear.Therefore,the aim of this study was to investigate whether pericytes took a protective effect on...

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Veröffentlicht in:Chinese medical journal 2014, Vol.127 (15), p.2808-2813
Hauptverfasser: Jing, Yingli, Wu, Qingbin, Yuan, Xiaochen, Li, Bingwei, Liu, Mingming, Zhang, Xiaoyan, Liu, Shuying, Li, Hongwei, Xiu, Ruijuan
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container_end_page 2813
container_issue 15
container_start_page 2808
container_title Chinese medical journal
container_volume 127
creator Jing, Yingli
Wu, Qingbin
Yuan, Xiaochen
Li, Bingwei
Liu, Mingming
Zhang, Xiaoyan
Liu, Shuying
Li, Hongwei
Xiu, Ruijuan
description Background Pericytes,located on microvessels,help to maintain vascular stability and blood-brain barrier integrity.The influence of pericytes on microvessels after spinal cord injury (SCI) is less clear.Therefore,the aim of this study was to investigate whether pericytes took a protective effect on microvessels in melatonin-treated SCI.Methods C57BL/6 mice were randomly divided into three groups:sham group,SCI group,and melatonin group (n=27per group).Functional recovery was evaluated using the Basso Mouse Scale.Motor neurons were observed using hematoxylin and eosin staining.Pericyte coverage was analyzed using immunofluorescence.Permeability of blood-spinal cord barrier (BSCB) was assessed by administration of Evan's Blue.Protein levels of occludin,aquaporin-4 (AQP4),angiopoietin-1 (Ang1),intercellular cell adhesion molecule-1 (ICAM-1),Bcl-2,and Bax were determined using Western blotting.Mimicking the pathological conditions of SCI,melatonin-treated primary pericytes were subjected to oxygenglucose deprivation/reperfusion (OGD/R).Secretion of Ang1 was analyzed using an enzyme-linked immunosorbent assay,and the expression of ICAM-1 was detected by immunofluorescence.Results Melatonin treatment improved locomotor functional outcome and rescued motor neurons.Pericyte coverage was significantly reduced after SCI; melatonin treatment alleviated the loss of pericyte coverage and rescued perfused microvessels 7 days after injury.The permeability of BSCB and loss of occludin were attenuated,and edema formation and upregulation of AQP4 were inhibited,after melatonin treatment.The expression of Ang1 and Bcl-2 was improved,while the expression of ICAM-1 and Bax was inhibited,in melatonin-treated SCl mice.Furthermore,the secretion of Ang1 was increased and the expression of ICAM-1 was inhibited in melatonin-treated pericytes after OGD/R.Conclusions Melatonin ameliorated the loss of blood vessels and disruption of BSCB to exert a protective effect on SCI,which might be mediated by increased pericyte coverage.The upregulation of Ang1 in pericytes could inhibit inflammation and apoptosis to protect the microvessels.
doi_str_mv 10.3760/cma.j.issn.0366-6999.20140858
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Ltd. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c329t-42b03673236293b7f6db7e94c69d5eacf0c36a4be95b8135f35395ce3af429083</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/85656X/85656X.jpg</thumbnail><link.rule.ids>314,780,784,864,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25146619$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jing, Yingli</creatorcontrib><creatorcontrib>Wu, Qingbin</creatorcontrib><creatorcontrib>Yuan, Xiaochen</creatorcontrib><creatorcontrib>Li, Bingwei</creatorcontrib><creatorcontrib>Liu, Mingming</creatorcontrib><creatorcontrib>Zhang, Xiaoyan</creatorcontrib><creatorcontrib>Liu, Shuying</creatorcontrib><creatorcontrib>Li, Hongwei</creatorcontrib><creatorcontrib>Xiu, Ruijuan</creatorcontrib><title>Microvascular protective role of pericytes in melatonin-treated spinal cord injury in the C57BL/6 mice</title><title>Chinese medical journal</title><addtitle>Chinese Medical Journal</addtitle><description>Background Pericytes,located on microvessels,help to maintain vascular stability and blood-brain barrier integrity.The influence of pericytes on microvessels after spinal cord injury (SCI) is less clear.Therefore,the aim of this study was to investigate whether pericytes took a protective effect on microvessels in melatonin-treated SCI.Methods C57BL/6 mice were randomly divided into three groups:sham group,SCI group,and melatonin group (n=27per group).Functional recovery was evaluated using the Basso Mouse Scale.Motor neurons were observed using hematoxylin and eosin staining.Pericyte coverage was analyzed using immunofluorescence.Permeability of blood-spinal cord barrier (BSCB) was assessed by administration of Evan's Blue.Protein levels of occludin,aquaporin-4 (AQP4),angiopoietin-1 (Ang1),intercellular cell adhesion molecule-1 (ICAM-1),Bcl-2,and Bax were determined using Western blotting.Mimicking the pathological conditions of SCI,melatonin-treated primary pericytes were subjected to oxygenglucose deprivation/reperfusion (OGD/R).Secretion of Ang1 was analyzed using an enzyme-linked immunosorbent assay,and the expression of ICAM-1 was detected by immunofluorescence.Results Melatonin treatment improved locomotor functional outcome and rescued motor neurons.Pericyte coverage was significantly reduced after SCI; melatonin treatment alleviated the loss of pericyte coverage and rescued perfused microvessels 7 days after injury.The permeability of BSCB and loss of occludin were attenuated,and edema formation and upregulation of AQP4 were inhibited,after melatonin treatment.The expression of Ang1 and Bcl-2 was improved,while the expression of ICAM-1 and Bax was inhibited,in melatonin-treated SCl mice.Furthermore,the secretion of Ang1 was increased and the expression of ICAM-1 was inhibited in melatonin-treated pericytes after OGD/R.Conclusions Melatonin ameliorated the loss of blood vessels and disruption of BSCB to exert a protective effect on SCI,which might be mediated by increased pericyte coverage.The upregulation of Ang1 in pericytes could inhibit inflammation and apoptosis to protect the microvessels.</description><subject>Angiopoietin-1 - metabolism</subject><subject>Animals</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>ICAM-1</subject><subject>Intercellular Adhesion Molecule-1 - metabolism</subject><subject>Male</subject><subject>Melatonin - pharmacology</subject><subject>Melatonin - therapeutic use</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microvessels - cytology</subject><subject>Occludin - metabolism</subject><subject>Pericytes - drug effects</subject><subject>Pericytes - metabolism</subject><subject>Random Allocation</subject><subject>Spinal Cord Injuries - drug therapy</subject><subject>Spinal Cord Injuries - metabolism</subject><subject>保护作用</subject><subject>小鼠</subject><subject>微血管</subject><subject>水通道蛋白4</subject><subject>激素治疗</subject><subject>细胞间黏附分子-1</subject><subject>脊髓损伤</subject><issn>0366-6999</issn><issn>2542-5641</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo90MtO3DAUBmCroipT2leorEqgbhJ8T7wsoxaQBrGh68hxThhHiT3YDmj69GQ0wOoszqdz-RE6p6TklSKXdjLlULqUfEm4UoXSWpeMUEFqWX9CKyYFK6QS9AStPsAp-prSQAiTslJf0CmTVChF9Qr1d87G8GySnUcT8S6GDDa7Z8AxjIBDj3cQnd1nSNh5PMFocvDOFzmCydDhtHPejNiG2C1gmOP-4PIW8FpWV5tLhSdn4Rv63Jsxwfe3eob-_f3zsL4pNvfXt-vfm8JypnMhWLvcXHHGFdO8rXrVtRVoYZXuJBjbE8uVES1o2daUy55LrqUFbnrBNKn5Gbo4zn0xvjf-sRnCHJf7UvN_a6fhkBOVhFYL_HWEy8dPM6TcTC5ZGEfjIcypoVJKxeqaHOiPNzq3E3TNLrrJxH3zHuICfh6B3Qb_-OSWte_m0NeSCcFfAdL2gpY</recordid><startdate>2014</startdate><enddate>2014</enddate><creator>Jing, Yingli</creator><creator>Wu, Qingbin</creator><creator>Yuan, Xiaochen</creator><creator>Li, Bingwei</creator><creator>Liu, Mingming</creator><creator>Zhang, Xiaoyan</creator><creator>Liu, Shuying</creator><creator>Li, Hongwei</creator><creator>Xiu, Ruijuan</creator><general>Institute of Microcirculation, Key Laboratory of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100005, China</general><scope>2RA</scope><scope>92L</scope><scope>CQIGP</scope><scope>W91</scope><scope>~WA</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>2B.</scope><scope>4A8</scope><scope>92I</scope><scope>93N</scope><scope>PSX</scope><scope>TCJ</scope></search><sort><creationdate>2014</creationdate><title>Microvascular protective role of pericytes in melatonin-treated spinal cord injury in the C57BL/6 mice</title><author>Jing, Yingli ; Wu, Qingbin ; Yuan, Xiaochen ; Li, Bingwei ; Liu, Mingming ; Zhang, Xiaoyan ; Liu, Shuying ; Li, Hongwei ; Xiu, Ruijuan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c329t-42b03673236293b7f6db7e94c69d5eacf0c36a4be95b8135f35395ce3af429083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Angiopoietin-1 - 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Academic</collection><collection>Wanfang Data Journals - Hong Kong</collection><collection>WANFANG Data Centre</collection><collection>Wanfang Data Journals</collection><collection>万方数据期刊 - 香港版</collection><collection>China Online Journals (COJ)</collection><collection>China Online Journals (COJ)</collection><jtitle>Chinese medical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jing, Yingli</au><au>Wu, Qingbin</au><au>Yuan, Xiaochen</au><au>Li, Bingwei</au><au>Liu, Mingming</au><au>Zhang, Xiaoyan</au><au>Liu, Shuying</au><au>Li, Hongwei</au><au>Xiu, Ruijuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Microvascular protective role of pericytes in melatonin-treated spinal cord injury in the C57BL/6 mice</atitle><jtitle>Chinese medical journal</jtitle><addtitle>Chinese Medical Journal</addtitle><date>2014</date><risdate>2014</risdate><volume>127</volume><issue>15</issue><spage>2808</spage><epage>2813</epage><pages>2808-2813</pages><issn>0366-6999</issn><eissn>2542-5641</eissn><abstract>Background Pericytes,located on microvessels,help to maintain vascular stability and blood-brain barrier integrity.The influence of pericytes on microvessels after spinal cord injury (SCI) is less clear.Therefore,the aim of this study was to investigate whether pericytes took a protective effect on microvessels in melatonin-treated SCI.Methods C57BL/6 mice were randomly divided into three groups:sham group,SCI group,and melatonin group (n=27per group).Functional recovery was evaluated using the Basso Mouse Scale.Motor neurons were observed using hematoxylin and eosin staining.Pericyte coverage was analyzed using immunofluorescence.Permeability of blood-spinal cord barrier (BSCB) was assessed by administration of Evan's Blue.Protein levels of occludin,aquaporin-4 (AQP4),angiopoietin-1 (Ang1),intercellular cell adhesion molecule-1 (ICAM-1),Bcl-2,and Bax were determined using Western blotting.Mimicking the pathological conditions of SCI,melatonin-treated primary pericytes were subjected to oxygenglucose deprivation/reperfusion (OGD/R).Secretion of Ang1 was analyzed using an enzyme-linked immunosorbent assay,and the expression of ICAM-1 was detected by immunofluorescence.Results Melatonin treatment improved locomotor functional outcome and rescued motor neurons.Pericyte coverage was significantly reduced after SCI; melatonin treatment alleviated the loss of pericyte coverage and rescued perfused microvessels 7 days after injury.The permeability of BSCB and loss of occludin were attenuated,and edema formation and upregulation of AQP4 were inhibited,after melatonin treatment.The expression of Ang1 and Bcl-2 was improved,while the expression of ICAM-1 and Bax was inhibited,in melatonin-treated SCl mice.Furthermore,the secretion of Ang1 was increased and the expression of ICAM-1 was inhibited in melatonin-treated pericytes after OGD/R.Conclusions Melatonin ameliorated the loss of blood vessels and disruption of BSCB to exert a protective effect on SCI,which might be mediated by increased pericyte coverage.The upregulation of Ang1 in pericytes could inhibit inflammation and apoptosis to protect the microvessels.</abstract><cop>China</cop><pub>Institute of Microcirculation, Key Laboratory of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100005, China</pub><pmid>25146619</pmid><doi>10.3760/cma.j.issn.0366-6999.20140858</doi><tpages>6</tpages></addata></record>
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subjects Angiopoietin-1 - metabolism
Animals
Enzyme-Linked Immunosorbent Assay
ICAM-1
Intercellular Adhesion Molecule-1 - metabolism
Male
Melatonin - pharmacology
Melatonin - therapeutic use
Mice
Mice, Inbred C57BL
Microvessels - cytology
Occludin - metabolism
Pericytes - drug effects
Pericytes - metabolism
Random Allocation
Spinal Cord Injuries - drug therapy
Spinal Cord Injuries - metabolism
保护作用
小鼠
微血管
水通道蛋白4
激素治疗
细胞间黏附分子-1
脊髓损伤
title Microvascular protective role of pericytes in melatonin-treated spinal cord injury in the C57BL/6 mice
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