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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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 & 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 - metabolism</topic><topic>Animals</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>ICAM-1</topic><topic>Intercellular Adhesion Molecule-1 - metabolism</topic><topic>Male</topic><topic>Melatonin - pharmacology</topic><topic>Melatonin - therapeutic use</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microvessels - cytology</topic><topic>Occludin - metabolism</topic><topic>Pericytes - drug effects</topic><topic>Pericytes - metabolism</topic><topic>Random Allocation</topic><topic>Spinal Cord Injuries - drug therapy</topic><topic>Spinal Cord Injuries - metabolism</topic><topic>保护作用</topic><topic>小鼠</topic><topic>微血管</topic><topic>水通道蛋白4</topic><topic>激素治疗</topic><topic>细胞间黏附分子-1</topic><topic>脊髓损伤</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><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><collection>中文科技期刊数据库</collection><collection>中文科技期刊数据库-CALIS站点</collection><collection>中文科技期刊数据库-7.0平台</collection><collection>中文科技期刊数据库-医药卫生</collection><collection>中文科技期刊数据库- 镜像站点</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - 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 & 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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