Bexarotene Enhances Macrophage Erythrophagocytosis and Hematoma Clearance in Experimental Intracerebral Hemorrhage
BACKGROUND AND PURPOSE—Enhancement of erythrophagocytosis by macrophages in a timely manner can limit the toxic effects of erythrocyte metabolites and promote brain recovery after intracerebral hemorrhage (ICH). In the current study, we investigated the therapeutic effect of retinoid X receptor agon...
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| Veröffentlicht in: | Stroke (1970) 2020-02, Vol.51 (2), p.612-618 |
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| container_title | Stroke (1970) |
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| creator | Chang, Che-Feng Massey, Jordan Osherov, Artem Angenendt da Costa, Luís Henrique Sansing, Lauren H. |
| description | BACKGROUND AND PURPOSE—Enhancement of erythrophagocytosis by macrophages in a timely manner can limit the toxic effects of erythrocyte metabolites and promote brain recovery after intracerebral hemorrhage (ICH). In the current study, we investigated the therapeutic effect of retinoid X receptor agonist, bexarotene, in facilitating erythrophagocytosis and neurobehavioral recovery in 2 mouse models of ICH.
METHODS—Bone marrow-derived macrophages and fluorescently labeled erythrocytes were used to study erythrophagocytosis in vitro with phenotypic changes quantified by gene expression. ICH was modeled in vivo using intrastriatal autologous blood and collagenase injection in mice with and without bexarotene treatment beginning 3 hours after ICH. In vivo phagocytosis, ability and hematoma clearance were evaluated by erythrophagocytosis assays, flow cytometry, and histological analysis. Neurological deficits and functional recovery were also quantified.
RESULTS—Bexarotene increased macrophage expression of phagocytosis receptors and erythrophagocytosis and reduced macrophage TNF (tumor necrosis factor) production in vitro. In vivo, bexarotene treatment enhanced erythrophagocytosis, reduced hematoma volume, and ultimately improved neurological recovery after ICH in 2 distinct models of ICH.
CONCLUSIONS—Bexarotene administration is beneficial for recovery after ICH by enhancing hemorrhage phagocytosis, modulating macrophage phenotype, and improving functional recovery. |
| doi_str_mv | 10.1161/STROKEAHA.119.027037 |
| format | Article |
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METHODS—Bone marrow-derived macrophages and fluorescently labeled erythrocytes were used to study erythrophagocytosis in vitro with phenotypic changes quantified by gene expression. ICH was modeled in vivo using intrastriatal autologous blood and collagenase injection in mice with and without bexarotene treatment beginning 3 hours after ICH. In vivo phagocytosis, ability and hematoma clearance were evaluated by erythrophagocytosis assays, flow cytometry, and histological analysis. Neurological deficits and functional recovery were also quantified.
RESULTS—Bexarotene increased macrophage expression of phagocytosis receptors and erythrophagocytosis and reduced macrophage TNF (tumor necrosis factor) production in vitro. In vivo, bexarotene treatment enhanced erythrophagocytosis, reduced hematoma volume, and ultimately improved neurological recovery after ICH in 2 distinct models of ICH.
CONCLUSIONS—Bexarotene administration is beneficial for recovery after ICH by enhancing hemorrhage phagocytosis, modulating macrophage phenotype, and improving functional recovery.</description><identifier>ISSN: 0039-2499</identifier><identifier>EISSN: 1524-4628</identifier><identifier>DOI: 10.1161/STROKEAHA.119.027037</identifier><identifier>PMID: 31826730</identifier><language>eng</language><publisher>United States: American Heart Association, Inc</publisher><subject>Animals ; Bexarotene - pharmacology ; Brain - drug effects ; Brain - pathology ; Cerebral Hemorrhage - drug therapy ; Disease Models, Animal ; Erythrocytes - drug effects ; Erythrocytes - pathology ; Hematoma - drug therapy ; Hematoma - metabolism ; Macrophages - drug effects ; Macrophages - metabolism ; Microglia - drug effects ; Phagocytosis - drug effects</subject><ispartof>Stroke (1970), 2020-02, Vol.51 (2), p.612-618</ispartof><rights>American Heart Association, Inc.</rights><rights>2020 American Heart Association, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5537-13319e09f2cd82f35b3ce82d88831b21494b2a2b80722a98dfffb54481dfaa413</citedby><cites>FETCH-LOGICAL-c5537-13319e09f2cd82f35b3ce82d88831b21494b2a2b80722a98dfffb54481dfaa413</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,3687,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31826730$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chang, Che-Feng</creatorcontrib><creatorcontrib>Massey, Jordan</creatorcontrib><creatorcontrib>Osherov, Artem</creatorcontrib><creatorcontrib>Angenendt da Costa, Luís Henrique</creatorcontrib><creatorcontrib>Sansing, Lauren H.</creatorcontrib><title>Bexarotene Enhances Macrophage Erythrophagocytosis and Hematoma Clearance in Experimental Intracerebral Hemorrhage</title><title>Stroke (1970)</title><addtitle>Stroke</addtitle><description>BACKGROUND AND PURPOSE—Enhancement of erythrophagocytosis by macrophages in a timely manner can limit the toxic effects of erythrocyte metabolites and promote brain recovery after intracerebral hemorrhage (ICH). In the current study, we investigated the therapeutic effect of retinoid X receptor agonist, bexarotene, in facilitating erythrophagocytosis and neurobehavioral recovery in 2 mouse models of ICH.
METHODS—Bone marrow-derived macrophages and fluorescently labeled erythrocytes were used to study erythrophagocytosis in vitro with phenotypic changes quantified by gene expression. ICH was modeled in vivo using intrastriatal autologous blood and collagenase injection in mice with and without bexarotene treatment beginning 3 hours after ICH. In vivo phagocytosis, ability and hematoma clearance were evaluated by erythrophagocytosis assays, flow cytometry, and histological analysis. Neurological deficits and functional recovery were also quantified.
RESULTS—Bexarotene increased macrophage expression of phagocytosis receptors and erythrophagocytosis and reduced macrophage TNF (tumor necrosis factor) production in vitro. In vivo, bexarotene treatment enhanced erythrophagocytosis, reduced hematoma volume, and ultimately improved neurological recovery after ICH in 2 distinct models of ICH.
CONCLUSIONS—Bexarotene administration is beneficial for recovery after ICH by enhancing hemorrhage phagocytosis, modulating macrophage phenotype, and improving functional recovery.</description><subject>Animals</subject><subject>Bexarotene - pharmacology</subject><subject>Brain - drug effects</subject><subject>Brain - pathology</subject><subject>Cerebral Hemorrhage - drug therapy</subject><subject>Disease Models, Animal</subject><subject>Erythrocytes - drug effects</subject><subject>Erythrocytes - pathology</subject><subject>Hematoma - drug therapy</subject><subject>Hematoma - metabolism</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - metabolism</subject><subject>Microglia - drug effects</subject><subject>Phagocytosis - drug effects</subject><issn>0039-2499</issn><issn>1524-4628</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkd1u1DAQhS1ERZfCGyCUF0gZ_2Rt3yAtq4WtaFUJyrU1SSZNIBuv7PRn3x5HgRW9KZIt69jzHY_mMPaOwznnS_7h-82366-b1XaVpD0HoUHqF2zBC6FytRTmJVsASJsLZe0pex3jTwAQ0hSv2KnkRiy1hAULn-gRgx9poGwztDhUFLMrrILft3ib7sJhbGfhq8PoYxczHOpsSzsc_Q6zdU8YJizrhmzzuKfQ7WgYsc8uhjFgRYHKkFQCfAiT5xt20mAf6e2f84z9-Ly5WW_zy-svF-vVZV4VhdQ5l5JbAtuIqjaikUUpKzKiNsZIXgqurCoFitKAFgKtqZumKQulDK8bRMXlGfs4--7vyh3VFU399G6fGsRwcB479_Rl6Fp36--d5rIwVicDNRukacQYqDmyHNyUgTtmkKR1cwYJe__vv0fo79BTgZkLHnw_Uoi_-rsHCq4l7Mf2f97qGTQFDHqpIRcgYFqQpy0L-RsIn6ib</recordid><startdate>202002</startdate><enddate>202002</enddate><creator>Chang, Che-Feng</creator><creator>Massey, Jordan</creator><creator>Osherov, Artem</creator><creator>Angenendt da Costa, Luís Henrique</creator><creator>Sansing, Lauren H.</creator><general>American Heart Association, 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>5PM</scope></search><sort><creationdate>202002</creationdate><title>Bexarotene Enhances Macrophage Erythrophagocytosis and Hematoma Clearance in Experimental Intracerebral Hemorrhage</title><author>Chang, Che-Feng ; Massey, Jordan ; Osherov, Artem ; Angenendt da Costa, Luís Henrique ; Sansing, Lauren H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5537-13319e09f2cd82f35b3ce82d88831b21494b2a2b80722a98dfffb54481dfaa413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Bexarotene - pharmacology</topic><topic>Brain - drug effects</topic><topic>Brain - pathology</topic><topic>Cerebral Hemorrhage - drug therapy</topic><topic>Disease Models, Animal</topic><topic>Erythrocytes - drug effects</topic><topic>Erythrocytes - pathology</topic><topic>Hematoma - drug therapy</topic><topic>Hematoma - metabolism</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - metabolism</topic><topic>Microglia - drug effects</topic><topic>Phagocytosis - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chang, Che-Feng</creatorcontrib><creatorcontrib>Massey, Jordan</creatorcontrib><creatorcontrib>Osherov, Artem</creatorcontrib><creatorcontrib>Angenendt da Costa, Luís Henrique</creatorcontrib><creatorcontrib>Sansing, Lauren H.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Stroke (1970)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chang, Che-Feng</au><au>Massey, Jordan</au><au>Osherov, Artem</au><au>Angenendt da Costa, Luís Henrique</au><au>Sansing, Lauren H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bexarotene Enhances Macrophage Erythrophagocytosis and Hematoma Clearance in Experimental Intracerebral Hemorrhage</atitle><jtitle>Stroke (1970)</jtitle><addtitle>Stroke</addtitle><date>2020-02</date><risdate>2020</risdate><volume>51</volume><issue>2</issue><spage>612</spage><epage>618</epage><pages>612-618</pages><issn>0039-2499</issn><eissn>1524-4628</eissn><abstract>BACKGROUND AND PURPOSE—Enhancement of erythrophagocytosis by macrophages in a timely manner can limit the toxic effects of erythrocyte metabolites and promote brain recovery after intracerebral hemorrhage (ICH). In the current study, we investigated the therapeutic effect of retinoid X receptor agonist, bexarotene, in facilitating erythrophagocytosis and neurobehavioral recovery in 2 mouse models of ICH.
METHODS—Bone marrow-derived macrophages and fluorescently labeled erythrocytes were used to study erythrophagocytosis in vitro with phenotypic changes quantified by gene expression. ICH was modeled in vivo using intrastriatal autologous blood and collagenase injection in mice with and without bexarotene treatment beginning 3 hours after ICH. In vivo phagocytosis, ability and hematoma clearance were evaluated by erythrophagocytosis assays, flow cytometry, and histological analysis. Neurological deficits and functional recovery were also quantified.
RESULTS—Bexarotene increased macrophage expression of phagocytosis receptors and erythrophagocytosis and reduced macrophage TNF (tumor necrosis factor) production in vitro. In vivo, bexarotene treatment enhanced erythrophagocytosis, reduced hematoma volume, and ultimately improved neurological recovery after ICH in 2 distinct models of ICH.
CONCLUSIONS—Bexarotene administration is beneficial for recovery after ICH by enhancing hemorrhage phagocytosis, modulating macrophage phenotype, and improving functional recovery.</abstract><cop>United States</cop><pub>American Heart Association, Inc</pub><pmid>31826730</pmid><doi>10.1161/STROKEAHA.119.027037</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Heart Association Journals; Journals@Ovid Complete; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Bexarotene - pharmacology Brain - drug effects Brain - pathology Cerebral Hemorrhage - drug therapy Disease Models, Animal Erythrocytes - drug effects Erythrocytes - pathology Hematoma - drug therapy Hematoma - metabolism Macrophages - drug effects Macrophages - metabolism Microglia - drug effects Phagocytosis - drug effects |
| title | Bexarotene Enhances Macrophage Erythrophagocytosis and Hematoma Clearance in Experimental Intracerebral Hemorrhage |
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