Imatinib enhances functional outcome after spinal cord injury
We investigated whether imatinib (Gleevec®, Novartis), a tyrosine kinase inhibitor, could improve functional outcome in experimental spinal cord injury. Rats subjected to contusion spinal cord injury were treated orally with imatinib for 5 days beginning 30 minutes after injury. We found that imatin...
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| Veröffentlicht in: | PloS one 2012-06, Vol.7 (6), p.e38760-e38760 |
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| creator | Abrams, Mathew B Nilsson, Ingrid Lewandowski, Sebastian A Kjell, Jacob Codeluppi, Simone Olson, Lars Eriksson, Ulf |
| description | We investigated whether imatinib (Gleevec®, Novartis), a tyrosine kinase inhibitor, could improve functional outcome in experimental spinal cord injury. Rats subjected to contusion spinal cord injury were treated orally with imatinib for 5 days beginning 30 minutes after injury. We found that imatinib significantly enhanced blood-spinal cord-barrier integrity, hindlimb locomotor function, sensorimotor integration, and bladder function, as well as attenuated astrogliosis and deposition of chondroitin sulfate proteoglycans, and increased tissue preservation. These improvements were associated with enhanced vascular integrity and reduced inflammation. Our results show that imatinib improves recovery in spinal cord injury by preserving axons and other spinal cord tissue components. The rapid time course of these beneficial effects suggests that the effects of imatinib are neuroprotective rather than neurorestorative. The positive effects on experimental spinal cord injury, obtained by oral delivery of a clinically used drug, makes imatinib an interesting candidate drug for clinical trials in spinal cord injury. |
| doi_str_mv | 10.1371/journal.pone.0038760 |
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Rats subjected to contusion spinal cord injury were treated orally with imatinib for 5 days beginning 30 minutes after injury. We found that imatinib significantly enhanced blood-spinal cord-barrier integrity, hindlimb locomotor function, sensorimotor integration, and bladder function, as well as attenuated astrogliosis and deposition of chondroitin sulfate proteoglycans, and increased tissue preservation. These improvements were associated with enhanced vascular integrity and reduced inflammation. Our results show that imatinib improves recovery in spinal cord injury by preserving axons and other spinal cord tissue components. The rapid time course of these beneficial effects suggests that the effects of imatinib are neuroprotective rather than neurorestorative. The positive effects on experimental spinal cord injury, obtained by oral delivery of a clinically used drug, makes imatinib an interesting candidate drug for clinical trials in spinal cord injury.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0038760</identifier><identifier>PMID: 22723886</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Angiogenesis ; Animals ; Antineoplastic agents ; Astrocytes - drug effects ; Astrocytes - metabolism ; Axons ; Benzamides ; Biochemistry ; Biology ; Biophysics ; Bladder ; Blood-brain barrier ; Blood-Brain Barrier - drug effects ; Chondroitin sulfate ; Chondroitin Sulfate Proteoglycans - metabolism ; Clinical trials ; Cysts ; Cytokines ; Cytotoxicity ; Disease Models, Animal ; Drug delivery systems ; Edema ; Enzyme inhibitors ; Evaluation ; Female ; Gliosis ; Hemorrhage ; Imatinib ; Imatinib Mesylate ; Inflammation ; Inflammation - drug therapy ; Inflammation - metabolism ; Injuries ; Integrity ; Localization ; Medical research ; Medicin och hälsovetenskap ; Medicine ; Mice ; Mice, Transgenic ; Motor Activity - drug effects ; Nervous system ; Neuroprotection ; Neurosciences ; Piperazines - administration & dosage ; Piperazines - pharmacology ; Preservation ; Protein Kinase Inhibitors - administration & dosage ; Protein Kinase Inhibitors - pharmacology ; Protein-tyrosine kinase ; Proteoglycans ; Pyrimidines - administration & dosage ; Pyrimidines - pharmacology ; Rats ; Receptors, Platelet-Derived Growth Factor - metabolism ; Recovery of Function - drug effects ; Rodents ; Sensorimotor integration ; Smooth muscle ; Spinal cord injuries ; Spinal Cord Injuries - drug therapy ; Spinal Cord Injuries - metabolism ; Spinal Cord Injuries - rehabilitation ; Sulfates ; Traumatic brain injury ; Treatment Outcome ; Tyrosine ; Urinary bladder ; Urine</subject><ispartof>PloS one, 2012-06, Vol.7 (6), p.e38760-e38760</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Abrams et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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>Abrams et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c897t-6f74eaf2ebf5c65b30c4a7bd9f3b5f923fdb793127c4615779de2444fff480c23</citedby><cites>FETCH-LOGICAL-c897t-6f74eaf2ebf5c65b30c4a7bd9f3b5f923fdb793127c4615779de2444fff480c23</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/PMC3378614/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378614/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,552,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22723886$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:124855938$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><contributor>Harvey, Alan R.</contributor><creatorcontrib>Abrams, Mathew B</creatorcontrib><creatorcontrib>Nilsson, Ingrid</creatorcontrib><creatorcontrib>Lewandowski, Sebastian A</creatorcontrib><creatorcontrib>Kjell, Jacob</creatorcontrib><creatorcontrib>Codeluppi, Simone</creatorcontrib><creatorcontrib>Olson, Lars</creatorcontrib><creatorcontrib>Eriksson, Ulf</creatorcontrib><title>Imatinib enhances functional outcome after spinal cord injury</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>We investigated whether imatinib (Gleevec®, Novartis), a tyrosine kinase inhibitor, could improve functional outcome in experimental spinal cord injury. Rats subjected to contusion spinal cord injury were treated orally with imatinib for 5 days beginning 30 minutes after injury. We found that imatinib significantly enhanced blood-spinal cord-barrier integrity, hindlimb locomotor function, sensorimotor integration, and bladder function, as well as attenuated astrogliosis and deposition of chondroitin sulfate proteoglycans, and increased tissue preservation. These improvements were associated with enhanced vascular integrity and reduced inflammation. Our results show that imatinib improves recovery in spinal cord injury by preserving axons and other spinal cord tissue components. The rapid time course of these beneficial effects suggests that the effects of imatinib are neuroprotective rather than neurorestorative. The positive effects on experimental spinal cord injury, obtained by oral delivery of a clinically used drug, makes imatinib an interesting candidate drug for clinical trials in spinal cord injury.</description><subject>Angiogenesis</subject><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Astrocytes - drug effects</subject><subject>Astrocytes - metabolism</subject><subject>Axons</subject><subject>Benzamides</subject><subject>Biochemistry</subject><subject>Biology</subject><subject>Biophysics</subject><subject>Bladder</subject><subject>Blood-brain barrier</subject><subject>Blood-Brain Barrier - drug effects</subject><subject>Chondroitin sulfate</subject><subject>Chondroitin Sulfate Proteoglycans - metabolism</subject><subject>Clinical trials</subject><subject>Cysts</subject><subject>Cytokines</subject><subject>Cytotoxicity</subject><subject>Disease Models, Animal</subject><subject>Drug delivery systems</subject><subject>Edema</subject><subject>Enzyme inhibitors</subject><subject>Evaluation</subject><subject>Female</subject><subject>Gliosis</subject><subject>Hemorrhage</subject><subject>Imatinib</subject><subject>Imatinib Mesylate</subject><subject>Inflammation</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation - metabolism</subject><subject>Injuries</subject><subject>Integrity</subject><subject>Localization</subject><subject>Medical research</subject><subject>Medicin och hälsovetenskap</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Motor Activity - drug effects</subject><subject>Nervous system</subject><subject>Neuroprotection</subject><subject>Neurosciences</subject><subject>Piperazines - administration & dosage</subject><subject>Piperazines - pharmacology</subject><subject>Preservation</subject><subject>Protein Kinase Inhibitors - administration & dosage</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Protein-tyrosine kinase</subject><subject>Proteoglycans</subject><subject>Pyrimidines - administration & dosage</subject><subject>Pyrimidines - pharmacology</subject><subject>Rats</subject><subject>Receptors, Platelet-Derived Growth Factor - metabolism</subject><subject>Recovery of Function - drug effects</subject><subject>Rodents</subject><subject>Sensorimotor integration</subject><subject>Smooth muscle</subject><subject>Spinal cord injuries</subject><subject>Spinal Cord Injuries - drug therapy</subject><subject>Spinal Cord Injuries - metabolism</subject><subject>Spinal Cord Injuries - rehabilitation</subject><subject>Sulfates</subject><subject>Traumatic brain injury</subject><subject>Treatment Outcome</subject><subject>Tyrosine</subject><subject>Urinary bladder</subject><subject>Urine</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>D8T</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7rr6D0QLgujFjPlqkl4oLIsfAwsLft2GND2Zydhpukmr7r83dTrrVlaQXjScPu8TcpqTZY8xWmIq8KutH0Krm2XnW1giRKXg6E52jEtKFpwgevfG-ih7EOMWoYJKzu9nR4QIQqXkx9nr1U73rnVVDu1GtwZibofW9M4nd-6H3vgd5Nr2EPLYubFofKhz126HcPUwu2d1E-HR9D7Jvrx7-_nsw-L84v3q7PR8YWQp-gW3goG2BCpbGF5UFBmmRVWXllaFLQm1dSVKiokwjONCiLIGwhiz1jKJDKEn2dO9t2t8VNPJo8KUcCxlgUQiVnui9nqruuB2Olwpr536XfBhrXTonWlA8bqmpYQCaY4Y4kgiy4oKUahLoLUdXYu9K_6Abqhmtqn0La1AFZRTRhNf_pPvgq__hA5BTJgsipLKlH0znWyodlAbaPugm7li9qV1G7X23xWlQnLMkuDFJAj-coDYq52LBppGt-CH1CNEcCmJQDyhz_5Cb-_kRK11apZrrU_7mlGqTplIngThRC1vodJTw86ZdCWtS_VZ4OUskJgefvZrPcSoVp8-_j978XXOPr_BbkA3_Sb6ZhhvcJyDbA-a4GMMYK-bjJEaJ-rQDTVOlJomKsWe3PxB16HDCNFfwXkb_g</recordid><startdate>20120619</startdate><enddate>20120619</enddate><creator>Abrams, Mathew B</creator><creator>Nilsson, Ingrid</creator><creator>Lewandowski, Sebastian A</creator><creator>Kjell, Jacob</creator><creator>Codeluppi, Simone</creator><creator>Olson, Lars</creator><creator>Eriksson, Ulf</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>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>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope><scope>DOA</scope></search><sort><creationdate>20120619</creationdate><title>Imatinib enhances functional outcome after spinal cord injury</title><author>Abrams, Mathew B ; Nilsson, Ingrid ; Lewandowski, Sebastian A ; Kjell, Jacob ; Codeluppi, Simone ; Olson, Lars ; Eriksson, Ulf</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c897t-6f74eaf2ebf5c65b30c4a7bd9f3b5f923fdb793127c4615779de2444fff480c23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Angiogenesis</topic><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Astrocytes - drug effects</topic><topic>Astrocytes - metabolism</topic><topic>Axons</topic><topic>Benzamides</topic><topic>Biochemistry</topic><topic>Biology</topic><topic>Biophysics</topic><topic>Bladder</topic><topic>Blood-brain barrier</topic><topic>Blood-Brain Barrier - drug effects</topic><topic>Chondroitin sulfate</topic><topic>Chondroitin Sulfate Proteoglycans - metabolism</topic><topic>Clinical trials</topic><topic>Cysts</topic><topic>Cytokines</topic><topic>Cytotoxicity</topic><topic>Disease Models, Animal</topic><topic>Drug delivery systems</topic><topic>Edema</topic><topic>Enzyme inhibitors</topic><topic>Evaluation</topic><topic>Female</topic><topic>Gliosis</topic><topic>Hemorrhage</topic><topic>Imatinib</topic><topic>Imatinib Mesylate</topic><topic>Inflammation</topic><topic>Inflammation - drug therapy</topic><topic>Inflammation - metabolism</topic><topic>Injuries</topic><topic>Integrity</topic><topic>Localization</topic><topic>Medical research</topic><topic>Medicin och hälsovetenskap</topic><topic>Medicine</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Motor Activity - 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Rats subjected to contusion spinal cord injury were treated orally with imatinib for 5 days beginning 30 minutes after injury. We found that imatinib significantly enhanced blood-spinal cord-barrier integrity, hindlimb locomotor function, sensorimotor integration, and bladder function, as well as attenuated astrogliosis and deposition of chondroitin sulfate proteoglycans, and increased tissue preservation. These improvements were associated with enhanced vascular integrity and reduced inflammation. Our results show that imatinib improves recovery in spinal cord injury by preserving axons and other spinal cord tissue components. The rapid time course of these beneficial effects suggests that the effects of imatinib are neuroprotective rather than neurorestorative. The positive effects on experimental spinal cord injury, obtained by oral delivery of a clinically used drug, makes imatinib an interesting candidate drug for clinical trials in spinal cord injury.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22723886</pmid><doi>10.1371/journal.pone.0038760</doi><tpages>e38760</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-06, Vol.7 (6), p.e38760-e38760 |
| issn | 1932-6203 1932-6203 |
| language | eng |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; PubMed; PLoS_OA刊; SWEPUB Freely available online; Free Full-Text Journals in Chemistry; EZB Electronic Journals Library |
| subjects | Angiogenesis Animals Antineoplastic agents Astrocytes - drug effects Astrocytes - metabolism Axons Benzamides Biochemistry Biology Biophysics Bladder Blood-brain barrier Blood-Brain Barrier - drug effects Chondroitin sulfate Chondroitin Sulfate Proteoglycans - metabolism Clinical trials Cysts Cytokines Cytotoxicity Disease Models, Animal Drug delivery systems Edema Enzyme inhibitors Evaluation Female Gliosis Hemorrhage Imatinib Imatinib Mesylate Inflammation Inflammation - drug therapy Inflammation - metabolism Injuries Integrity Localization Medical research Medicin och hälsovetenskap Medicine Mice Mice, Transgenic Motor Activity - drug effects Nervous system Neuroprotection Neurosciences Piperazines - administration & dosage Piperazines - pharmacology Preservation Protein Kinase Inhibitors - administration & dosage Protein Kinase Inhibitors - pharmacology Protein-tyrosine kinase Proteoglycans Pyrimidines - administration & dosage Pyrimidines - pharmacology Rats Receptors, Platelet-Derived Growth Factor - metabolism Recovery of Function - drug effects Rodents Sensorimotor integration Smooth muscle Spinal cord injuries Spinal Cord Injuries - drug therapy Spinal Cord Injuries - metabolism Spinal Cord Injuries - rehabilitation Sulfates Traumatic brain injury Treatment Outcome Tyrosine Urinary bladder Urine |
| title | Imatinib enhances functional outcome after spinal cord injury |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T05%3A23%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Imatinib%20enhances%20functional%20outcome%20after%20spinal%20cord%20injury&rft.jtitle=PloS%20one&rft.au=Abrams,%20Mathew%20B&rft.date=2012-06-19&rft.volume=7&rft.issue=6&rft.spage=e38760&rft.epage=e38760&rft.pages=e38760-e38760&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0038760&rft_dat=%3Cgale_plos_%3EA477065071%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1326188507&rft_id=info:pmid/22723886&rft_galeid=A477065071&rft_doaj_id=oai_doaj_org_article_6dd398e50a60406080f45b03ed9e3df7&rfr_iscdi=true |