Curcumin attenuates blood-brain barrier disruption after subarachnoid hemorrhage in mice
Abstract Background Early brain injury (EBI), one of the most important mechanisms underlying subarachnoid hemorrhage (SAH), comprises edema formation and blood-brain barrier (BBB) disruption. Curcumin, an active extract from the rhizomes of Curcuma longa, alleviates neuroinflammation by as yet unkn...
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description | Abstract Background Early brain injury (EBI), one of the most important mechanisms underlying subarachnoid hemorrhage (SAH), comprises edema formation and blood-brain barrier (BBB) disruption. Curcumin, an active extract from the rhizomes of Curcuma longa, alleviates neuroinflammation by as yet unknown neuroprotective mechanisms. In this study, we examined whether curcumin treatment ameliorates SAH-induced brain edema and BBB permeability changes, as well as the mechanisms underlying this phenomenon. Methods We induced SAH in mice via endovascular perforation, administered curcumin 15 mins after surgery and evaluated neurological scores, brain water content, Evans blue extravasation, Western blot assay results and immunohistochemical analysis results 24 hours after surgery. Results Curcumin significantly improved neurological scores and reduced brain water content in treated mice compared with SAH mice. Furthermore, curcumin decreased Evans blue extravasation, matrix metallopeptidase (MMP)-9 expression, and the number of Iba-1-positive microglia in treated mice compared with SAH mice. Lastly, curcumin treatment increased the expression of the tight junction (TJ) proteins zonula occludens-1 (ZO-1) and Occludin in treated mice compared with vehicle-treated and sample SAH mice. Conclusion We demonstrated that curcumin inhibits microglial activation and MMP-9 expression, thereby reducing brain edema and attenuating post-SAH BBB disruption in mice. |
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Curcumin, an active extract from the rhizomes of Curcuma longa, alleviates neuroinflammation by as yet unknown neuroprotective mechanisms. In this study, we examined whether curcumin treatment ameliorates SAH-induced brain edema and BBB permeability changes, as well as the mechanisms underlying this phenomenon. Methods We induced SAH in mice via endovascular perforation, administered curcumin 15 mins after surgery and evaluated neurological scores, brain water content, Evans blue extravasation, Western blot assay results and immunohistochemical analysis results 24 hours after surgery. Results Curcumin significantly improved neurological scores and reduced brain water content in treated mice compared with SAH mice. Furthermore, curcumin decreased Evans blue extravasation, matrix metallopeptidase (MMP)-9 expression, and the number of Iba-1-positive microglia in treated mice compared with SAH mice. Lastly, curcumin treatment increased the expression of the tight junction (TJ) proteins zonula occludens-1 (ZO-1) and Occludin in treated mice compared with vehicle-treated and sample SAH mice. Conclusion We demonstrated that curcumin inhibits microglial activation and MMP-9 expression, thereby reducing brain edema and attenuating post-SAH BBB disruption in mice.</description><identifier>ISSN: 0022-4804</identifier><identifier>EISSN: 1095-8673</identifier><identifier>DOI: 10.1016/j.jss.2016.08.090</identifier><identifier>PMID: 27979493</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Biomarkers - metabolism ; Blood-brain barrier ; Blood-Brain Barrier - drug effects ; Blood-Brain Barrier - metabolism ; Blotting, Western ; Brain Edema - etiology ; Brain Edema - metabolism ; Brain Edema - prevention & control ; Curcumin ; Curcumin - pharmacology ; Curcumin - therapeutic use ; Early brain injury ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred C57BL ; Neuroprotective Agents - pharmacology ; Neuroprotective Agents - therapeutic use ; Subarachnoid hemorrhage ; Subarachnoid Hemorrhage - complications ; Subarachnoid Hemorrhage - drug therapy ; Subarachnoid Hemorrhage - metabolism ; Surgery ; Treatment Outcome</subject><ispartof>The Journal of surgical research, 2017-01, Vol.207, p.85-91</ispartof><rights>2016 Elsevier Inc.</rights><rights>Copyright © 2016 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-ac7ca72061c9b7267e8a4fae1262238a296741d8fdb80717d0ad5ebc4e299e3</citedby><cites>FETCH-LOGICAL-c408t-ac7ca72061c9b7267e8a4fae1262238a296741d8fdb80717d0ad5ebc4e299e3</cites><orcidid>0000-0002-3577-8109</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jss.2016.08.090$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27979493$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yuan, Jichao</creatorcontrib><creatorcontrib>Liu, Wei</creatorcontrib><creatorcontrib>Zhu, Haitao</creatorcontrib><creatorcontrib>Zhang, Xuan</creatorcontrib><creatorcontrib>Feng, Yang</creatorcontrib><creatorcontrib>Chen, Yaxing</creatorcontrib><creatorcontrib>Feng, Hua</creatorcontrib><creatorcontrib>Lin, Jiangkai</creatorcontrib><title>Curcumin attenuates blood-brain barrier disruption after subarachnoid hemorrhage in mice</title><title>The Journal of surgical research</title><addtitle>J Surg Res</addtitle><description>Abstract Background Early brain injury (EBI), one of the most important mechanisms underlying subarachnoid hemorrhage (SAH), comprises edema formation and blood-brain barrier (BBB) disruption. Curcumin, an active extract from the rhizomes of Curcuma longa, alleviates neuroinflammation by as yet unknown neuroprotective mechanisms. In this study, we examined whether curcumin treatment ameliorates SAH-induced brain edema and BBB permeability changes, as well as the mechanisms underlying this phenomenon. Methods We induced SAH in mice via endovascular perforation, administered curcumin 15 mins after surgery and evaluated neurological scores, brain water content, Evans blue extravasation, Western blot assay results and immunohistochemical analysis results 24 hours after surgery. Results Curcumin significantly improved neurological scores and reduced brain water content in treated mice compared with SAH mice. Furthermore, curcumin decreased Evans blue extravasation, matrix metallopeptidase (MMP)-9 expression, and the number of Iba-1-positive microglia in treated mice compared with SAH mice. Lastly, curcumin treatment increased the expression of the tight junction (TJ) proteins zonula occludens-1 (ZO-1) and Occludin in treated mice compared with vehicle-treated and sample SAH mice. Conclusion We demonstrated that curcumin inhibits microglial activation and MMP-9 expression, thereby reducing brain edema and attenuating post-SAH BBB disruption in mice.</description><subject>Animals</subject><subject>Biomarkers - metabolism</subject><subject>Blood-brain barrier</subject><subject>Blood-Brain Barrier - drug effects</subject><subject>Blood-Brain Barrier - metabolism</subject><subject>Blotting, Western</subject><subject>Brain Edema - etiology</subject><subject>Brain Edema - metabolism</subject><subject>Brain Edema - prevention & control</subject><subject>Curcumin</subject><subject>Curcumin - pharmacology</subject><subject>Curcumin - therapeutic use</subject><subject>Early brain injury</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Neuroprotective Agents - therapeutic use</subject><subject>Subarachnoid hemorrhage</subject><subject>Subarachnoid Hemorrhage - complications</subject><subject>Subarachnoid Hemorrhage - drug therapy</subject><subject>Subarachnoid Hemorrhage - metabolism</subject><subject>Surgery</subject><subject>Treatment Outcome</subject><issn>0022-4804</issn><issn>1095-8673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU2LFDEQhoMo7rj6A7xIH710W0l68oEgyOAXLHhYD95COql20nZ3xqSzsP_eDLN68OAplar3faGeIuQlhY4CFW-mbsq5Y7XsQHWg4RHZUdD7VgnJH5MdAGNtr6C_Is9ynqD-teRPyRWTWupe8x35fijJlSWsjd02XIvdMDfDHKNvh2Rre7ApBUyNDzmV0xZiVY5bbeRSR9Yd1xh8c8QlpnS0P7CpniU4fE6ejHbO-OLhvSa3Hz98O3xub75--nJ4f9O6HtTWWiedlQwEdXqQTEhUth8tUiYY48oyLWRPvRr9oEBS6cH6PQ6uR6Y18mvy-pJ6SvFXwbyZJWSH82xXjCUbqvZMqF7sZZXSi9SlmHPC0ZxSWGy6NxTMGaeZTMVpzjgNKFNxVs-rh_gyLOj_Ov7wq4K3FwHWFe8qJ5NdwNWhDwndZnwM_41_94_bzWENzs4_8R7zFEtaKztDTWYGzO35nudzUsGBC674b08Fm-Y</recordid><startdate>20170101</startdate><enddate>20170101</enddate><creator>Yuan, Jichao</creator><creator>Liu, Wei</creator><creator>Zhu, Haitao</creator><creator>Zhang, Xuan</creator><creator>Feng, Yang</creator><creator>Chen, Yaxing</creator><creator>Feng, Hua</creator><creator>Lin, Jiangkai</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3577-8109</orcidid></search><sort><creationdate>20170101</creationdate><title>Curcumin attenuates blood-brain barrier disruption after subarachnoid hemorrhage in mice</title><author>Yuan, Jichao ; Liu, Wei ; Zhu, Haitao ; Zhang, Xuan ; Feng, Yang ; Chen, Yaxing ; Feng, Hua ; Lin, Jiangkai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-ac7ca72061c9b7267e8a4fae1262238a296741d8fdb80717d0ad5ebc4e299e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Biomarkers - metabolism</topic><topic>Blood-brain barrier</topic><topic>Blood-Brain Barrier - drug effects</topic><topic>Blood-Brain Barrier - metabolism</topic><topic>Blotting, Western</topic><topic>Brain Edema - etiology</topic><topic>Brain Edema - metabolism</topic><topic>Brain Edema - prevention & control</topic><topic>Curcumin</topic><topic>Curcumin - pharmacology</topic><topic>Curcumin - therapeutic use</topic><topic>Early brain injury</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Neuroprotective Agents - therapeutic use</topic><topic>Subarachnoid hemorrhage</topic><topic>Subarachnoid Hemorrhage - complications</topic><topic>Subarachnoid Hemorrhage - drug therapy</topic><topic>Subarachnoid Hemorrhage - metabolism</topic><topic>Surgery</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yuan, Jichao</creatorcontrib><creatorcontrib>Liu, Wei</creatorcontrib><creatorcontrib>Zhu, Haitao</creatorcontrib><creatorcontrib>Zhang, Xuan</creatorcontrib><creatorcontrib>Feng, Yang</creatorcontrib><creatorcontrib>Chen, Yaxing</creatorcontrib><creatorcontrib>Feng, Hua</creatorcontrib><creatorcontrib>Lin, Jiangkai</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of surgical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yuan, Jichao</au><au>Liu, Wei</au><au>Zhu, Haitao</au><au>Zhang, Xuan</au><au>Feng, Yang</au><au>Chen, Yaxing</au><au>Feng, Hua</au><au>Lin, Jiangkai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Curcumin attenuates blood-brain barrier disruption after subarachnoid hemorrhage in mice</atitle><jtitle>The Journal of surgical research</jtitle><addtitle>J Surg Res</addtitle><date>2017-01-01</date><risdate>2017</risdate><volume>207</volume><spage>85</spage><epage>91</epage><pages>85-91</pages><issn>0022-4804</issn><eissn>1095-8673</eissn><abstract>Abstract Background Early brain injury (EBI), one of the most important mechanisms underlying subarachnoid hemorrhage (SAH), comprises edema formation and blood-brain barrier (BBB) disruption. Curcumin, an active extract from the rhizomes of Curcuma longa, alleviates neuroinflammation by as yet unknown neuroprotective mechanisms. In this study, we examined whether curcumin treatment ameliorates SAH-induced brain edema and BBB permeability changes, as well as the mechanisms underlying this phenomenon. Methods We induced SAH in mice via endovascular perforation, administered curcumin 15 mins after surgery and evaluated neurological scores, brain water content, Evans blue extravasation, Western blot assay results and immunohistochemical analysis results 24 hours after surgery. Results Curcumin significantly improved neurological scores and reduced brain water content in treated mice compared with SAH mice. Furthermore, curcumin decreased Evans blue extravasation, matrix metallopeptidase (MMP)-9 expression, and the number of Iba-1-positive microglia in treated mice compared with SAH mice. Lastly, curcumin treatment increased the expression of the tight junction (TJ) proteins zonula occludens-1 (ZO-1) and Occludin in treated mice compared with vehicle-treated and sample SAH mice. Conclusion We demonstrated that curcumin inhibits microglial activation and MMP-9 expression, thereby reducing brain edema and attenuating post-SAH BBB disruption in mice.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>27979493</pmid><doi>10.1016/j.jss.2016.08.090</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-3577-8109</orcidid></addata></record> |
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subjects | Animals Biomarkers - metabolism Blood-brain barrier Blood-Brain Barrier - drug effects Blood-Brain Barrier - metabolism Blotting, Western Brain Edema - etiology Brain Edema - metabolism Brain Edema - prevention & control Curcumin Curcumin - pharmacology Curcumin - therapeutic use Early brain injury Immunohistochemistry Male Mice Mice, Inbred C57BL Neuroprotective Agents - pharmacology Neuroprotective Agents - therapeutic use Subarachnoid hemorrhage Subarachnoid Hemorrhage - complications Subarachnoid Hemorrhage - drug therapy Subarachnoid Hemorrhage - metabolism Surgery Treatment Outcome |
title | Curcumin attenuates blood-brain barrier disruption after subarachnoid hemorrhage in mice |
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