Efficacy of deferoxamine in animal models of intracerebral hemorrhage: a systematic review and stratified meta-analysis
Intracerebral hemorrhage (ICH) is a subtype of stroke associated with high morbidity and mortality rates. No proven treatments are available for this condition. Iron-mediated free radical injury is associated with secondary damage following ICH. Deferoxamine (DFX), a ferric-iron chelator, is a candi...
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| description | Intracerebral hemorrhage (ICH) is a subtype of stroke associated with high morbidity and mortality rates. No proven treatments are available for this condition. Iron-mediated free radical injury is associated with secondary damage following ICH. Deferoxamine (DFX), a ferric-iron chelator, is a candidate drug for the treatment of ICH. We performed a systematic review of studies involving the administration of DFX following ICH. In total, 20 studies were identified that described the efficacy of DFX in animal models of ICH and assessed changes in the brain water content, neurobehavioral score, or both. DFX reduced the brain water content by 85.7% in animal models of ICH (-0.86, 95% CI: -.48- -0.23; P < 0.01; 23 comparisons), and improved the neurobehavioral score by -1.08 (95% CI: -1.23- -0.92; P < 0.01; 62 comparisons). DFX was most efficacious when administered 2-4 h after ICH at a dose of 10-50 mg/kg depending on species, and this beneficial effect remained for up to 24 h postinjury. The efficacy was higher with phenobarbital anesthesia, intramuscular injection, and lysed erythrocyte infusion, and in Fischer 344 rats or aged animals. Overall, although DFX was found to be effective in experimental ICH, additional confirmation is needed due to possible publication bias, poor study quality, and the limited number of studies conducting clinical trials. |
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No proven treatments are available for this condition. Iron-mediated free radical injury is associated with secondary damage following ICH. Deferoxamine (DFX), a ferric-iron chelator, is a candidate drug for the treatment of ICH. We performed a systematic review of studies involving the administration of DFX following ICH. In total, 20 studies were identified that described the efficacy of DFX in animal models of ICH and assessed changes in the brain water content, neurobehavioral score, or both. DFX reduced the brain water content by 85.7% in animal models of ICH (-0.86, 95% CI: -.48- -0.23; P < 0.01; 23 comparisons), and improved the neurobehavioral score by -1.08 (95% CI: -1.23- -0.92; P < 0.01; 62 comparisons). DFX was most efficacious when administered 2-4 h after ICH at a dose of 10-50 mg/kg depending on species, and this beneficial effect remained for up to 24 h postinjury. The efficacy was higher with phenobarbital anesthesia, intramuscular injection, and lysed erythrocyte infusion, and in Fischer 344 rats or aged animals. Overall, although DFX was found to be effective in experimental ICH, additional confirmation is needed due to possible publication bias, poor study quality, and the limited number of studies conducting clinical trials.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0127256</identifier><identifier>PMID: 26000830</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Anesthesia ; Animal models ; Animals ; Brain ; Cerebral Hemorrhage - drug therapy ; Clinical trials ; Deferoxamine ; Deferoxamine - therapeutic use ; Disease Models, Animal ; Drug dosages ; Drug therapy ; Edema ; Effectiveness ; Erythrocytes ; Health aspects ; Hemorrhage ; Hospitals ; Integrative medicine ; Intracerebral hemorrhage ; Iron ; Medical research ; Medicine ; Meta-analysis ; Mice ; Moisture content ; Morbidity ; Neurology ; Patient outcomes ; Pharmacological research ; Phenobarbital ; Precision medicine ; Rats ; Rodents ; Siderophores - therapeutic use ; Standard deviation ; Stroke ; Studies ; Swine ; Systematic review ; Traumatic brain injury ; Treatment Outcome ; Water content</subject><ispartof>PloS one, 2015-05, Vol.10 (5), p.e0127256-e0127256</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Cui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Cui et al 2015 Cui et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-3d2f2638019413af9cd5cc6a83310b27104ab155a14ccab30097fde506ece633</citedby><cites>FETCH-LOGICAL-c692t-3d2f2638019413af9cd5cc6a83310b27104ab155a14ccab30097fde506ece633</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441464/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441464/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26000830$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cui, Han-Jin</creatorcontrib><creatorcontrib>He, Hao-yu</creatorcontrib><creatorcontrib>Yang, A-Li</creatorcontrib><creatorcontrib>Zhou, Hua-Jun</creatorcontrib><creatorcontrib>Wang, Cong</creatorcontrib><creatorcontrib>Luo, Jie-Kun</creatorcontrib><creatorcontrib>Lin, Yuan</creatorcontrib><creatorcontrib>Tang, Tao</creatorcontrib><title>Efficacy of deferoxamine in animal models of intracerebral hemorrhage: a systematic review and stratified meta-analysis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Intracerebral hemorrhage (ICH) is a subtype of stroke associated with high morbidity and mortality rates. No proven treatments are available for this condition. Iron-mediated free radical injury is associated with secondary damage following ICH. Deferoxamine (DFX), a ferric-iron chelator, is a candidate drug for the treatment of ICH. We performed a systematic review of studies involving the administration of DFX following ICH. In total, 20 studies were identified that described the efficacy of DFX in animal models of ICH and assessed changes in the brain water content, neurobehavioral score, or both. DFX reduced the brain water content by 85.7% in animal models of ICH (-0.86, 95% CI: -.48- -0.23; P < 0.01; 23 comparisons), and improved the neurobehavioral score by -1.08 (95% CI: -1.23- -0.92; P < 0.01; 62 comparisons). DFX was most efficacious when administered 2-4 h after ICH at a dose of 10-50 mg/kg depending on species, and this beneficial effect remained for up to 24 h postinjury. The efficacy was higher with phenobarbital anesthesia, intramuscular injection, and lysed erythrocyte infusion, and in Fischer 344 rats or aged animals. Overall, although DFX was found to be effective in experimental ICH, additional confirmation is needed due to possible publication bias, poor study quality, and the limited number of studies conducting clinical trials.</description><subject>Analysis</subject><subject>Anesthesia</subject><subject>Animal models</subject><subject>Animals</subject><subject>Brain</subject><subject>Cerebral Hemorrhage - drug therapy</subject><subject>Clinical trials</subject><subject>Deferoxamine</subject><subject>Deferoxamine - therapeutic use</subject><subject>Disease Models, Animal</subject><subject>Drug dosages</subject><subject>Drug therapy</subject><subject>Edema</subject><subject>Effectiveness</subject><subject>Erythrocytes</subject><subject>Health aspects</subject><subject>Hemorrhage</subject><subject>Hospitals</subject><subject>Integrative medicine</subject><subject>Intracerebral hemorrhage</subject><subject>Iron</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Meta-analysis</subject><subject>Mice</subject><subject>Moisture content</subject><subject>Morbidity</subject><subject>Neurology</subject><subject>Patient outcomes</subject><subject>Pharmacological research</subject><subject>Phenobarbital</subject><subject>Precision medicine</subject><subject>Rats</subject><subject>Rodents</subject><subject>Siderophores - therapeutic use</subject><subject>Standard deviation</subject><subject>Stroke</subject><subject>Studies</subject><subject>Swine</subject><subject>Systematic review</subject><subject>Traumatic brain injury</subject><subject>Treatment Outcome</subject><subject>Water content</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk01v1DAQhiMEomXhHyCIhITgsIu_4mQ5IFVVgZUqVYKKqzVxxrteJXFrJ2333-N002qDekA-2Bo_72vP2JMkbylZUJ7TL1vX-xbqxZVrcUEoy1kmnyXHdMnZXDLCnx-sj5JXIWwJyXgh5cvkiElCSMHJcXJ7ZozVoHepM2mFBr27g8a2mNo2hdY2UKeNq7AOA2DbzoNGj6WP8Q02zvsNrPFrCmnYhQ4b6KxOPd5YvI3yKg1R0FljsUob7GAO8cq7YMPr5IWBOuCbcZ4ll9_PLk9_zs8vfqxOT87nWi5ZN-cVM0zygtCloBzMUleZ1hIKzikpWU6JgJJmGVChNZSckGVuKsyIRI2S81nyfm97VbugxpIFRWXBZJZTKiOx2hOVg6268jFjv1MOrLoPOL9W4GNSNSpSFqYAqgUjRkhdllpXOssyhlxAZQavb-NpfdlgpXEoVz0xne60dqPW7kYJIaiQIhp8Gg28u-4xdKqxQWNdQ4uuv783z_KBjOiHf9CnsxupNcQEbGvc8ICDqToRnHHGWPwHs2TxBBVHhY3V8X8ZG-MTweeJIDId3nVr6ENQq9-__p-9-DNlPx6wG4S62wRX9511bZiCYg9q70LwaB6LTIka2uOhGmpoDzW2R5S9O3ygR9FDP_C_2ZoLxQ</recordid><startdate>20150522</startdate><enddate>20150522</enddate><creator>Cui, Han-Jin</creator><creator>He, Hao-yu</creator><creator>Yang, A-Li</creator><creator>Zhou, Hua-Jun</creator><creator>Wang, Cong</creator><creator>Luo, Jie-Kun</creator><creator>Lin, Yuan</creator><creator>Tang, Tao</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150522</creationdate><title>Efficacy of deferoxamine in animal models of intracerebral hemorrhage: a systematic review and stratified meta-analysis</title><author>Cui, Han-Jin ; He, Hao-yu ; Yang, A-Li ; Zhou, Hua-Jun ; Wang, Cong ; Luo, Jie-Kun ; Lin, Yuan ; Tang, Tao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-3d2f2638019413af9cd5cc6a83310b27104ab155a14ccab30097fde506ece633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Analysis</topic><topic>Anesthesia</topic><topic>Animal models</topic><topic>Animals</topic><topic>Brain</topic><topic>Cerebral Hemorrhage - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cui, Han-Jin</au><au>He, Hao-yu</au><au>Yang, A-Li</au><au>Zhou, Hua-Jun</au><au>Wang, Cong</au><au>Luo, Jie-Kun</au><au>Lin, Yuan</au><au>Tang, Tao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy of deferoxamine in animal models of intracerebral hemorrhage: a systematic review and stratified meta-analysis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-05-22</date><risdate>2015</risdate><volume>10</volume><issue>5</issue><spage>e0127256</spage><epage>e0127256</epage><pages>e0127256-e0127256</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Intracerebral hemorrhage (ICH) is a subtype of stroke associated with high morbidity and mortality rates. No proven treatments are available for this condition. Iron-mediated free radical injury is associated with secondary damage following ICH. Deferoxamine (DFX), a ferric-iron chelator, is a candidate drug for the treatment of ICH. We performed a systematic review of studies involving the administration of DFX following ICH. In total, 20 studies were identified that described the efficacy of DFX in animal models of ICH and assessed changes in the brain water content, neurobehavioral score, or both. DFX reduced the brain water content by 85.7% in animal models of ICH (-0.86, 95% CI: -.48- -0.23; P < 0.01; 23 comparisons), and improved the neurobehavioral score by -1.08 (95% CI: -1.23- -0.92; P < 0.01; 62 comparisons). DFX was most efficacious when administered 2-4 h after ICH at a dose of 10-50 mg/kg depending on species, and this beneficial effect remained for up to 24 h postinjury. The efficacy was higher with phenobarbital anesthesia, intramuscular injection, and lysed erythrocyte infusion, and in Fischer 344 rats or aged animals. Overall, although DFX was found to be effective in experimental ICH, additional confirmation is needed due to possible publication bias, poor study quality, and the limited number of studies conducting clinical trials.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26000830</pmid><doi>10.1371/journal.pone.0127256</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Analysis Anesthesia Animal models Animals Brain Cerebral Hemorrhage - drug therapy Clinical trials Deferoxamine Deferoxamine - therapeutic use Disease Models, Animal Drug dosages Drug therapy Edema Effectiveness Erythrocytes Health aspects Hemorrhage Hospitals Integrative medicine Intracerebral hemorrhage Iron Medical research Medicine Meta-analysis Mice Moisture content Morbidity Neurology Patient outcomes Pharmacological research Phenobarbital Precision medicine Rats Rodents Siderophores - therapeutic use Standard deviation Stroke Studies Swine Systematic review Traumatic brain injury Treatment Outcome Water content |
| title | Efficacy of deferoxamine in animal models of intracerebral hemorrhage: a systematic review and stratified meta-analysis |
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