Small Molecule Selectin Inhibitor in Global Cerebral Ischemia and Controlled Hemorrhagic Shock
BACKGROUND:The clinical and experimental management of stroke has not reached the therapeutic success seen in other medical conditions associated with ischemia/reperfusion. In this work, we investigated the effect of a small molecule selectin inhibitor TBC-1269, in animals subjected to global cerebr...
Gespeichert in:
| Veröffentlicht in: | The Journal of trauma, injury, infection, and critical care injury, infection, and critical care, 2008-09, Vol.65 (3), p.678-684 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 684 |
|---|---|
| container_issue | 3 |
| container_start_page | 678 |
| container_title | The Journal of trauma, injury, infection, and critical care |
| container_volume | 65 |
| creator | Anaya-Prado, Roberto Pérez-Gomez, Nahum Toledo-Pereyra, Luis H. Walsh, John Jordan, Jackie Ward, Peter A. |
| description | BACKGROUND:The clinical and experimental management of stroke has not reached the therapeutic success seen in other medical conditions associated with ischemia/reperfusion. In this work, we investigated the effect of a small molecule selectin inhibitor TBC-1269, in animals subjected to global cerebral ischemia (GCI) and controlled hemorrhagic shock (CHS).
METHODS:Forty-eight male Sprague-Dawley rats weighting between 275 g and 300 g were subjected to a model of GCI and CHS. Three groups of animals were included in this study (n = 16 per group)sham/saline (group 1); GCI/CHS/Saline (group 2); GCI/CHS/TBC-1269 (group 3). Experimental design consisted of bilateral carotid artery occlusion for 20 minutes, and the development of CHS until a mean arterial pressure of 50 mm Hg was reached. At 20 minutes, clamps were released, and resuscitation was achieved with normal saline, and the end point was to attain a mean arterial pressure of 80 mm Hg. Treatment at the beginning of resuscitation included either normal saline (groups 1 and 2) or TBC-1269 (25 mg/kg, group 3). The following indices were evaluatedbrain tissue myeloperoxidase, average numbers of ischemic neurons, and 7-day survival.
RESULTS:Brain myeloperoxidase was decreased in animals treated with TBC-1269, although this difference was not statistically significant. Treated animals demonstrated a significant smaller amount of ischemic neurons than the controls. Survival was also improved from 40% in controls to 80% with TBC-1269 treatment. This difference was statistically significant.
CONCLUSION:The use of a small molecule selectin inhibitor, TBC-1269, had a protective effect in this model of GCI and CHS, as evidenced by decreased numbers of ischemic neurons and improved survival rates. |
| doi_str_mv | 10.1097/TA.0b013e3181843f3a |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_69533553</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>69533553</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4484-5a3d4ca4624c1058341c366de0419baefd837a67b3c50f627ffc993a202cd5fd3</originalsourceid><addsrcrecordid>eNpdkUFv1DAQhS0EosvCL0BCucAtZeyxE-e4WpV2pSIOu1yxHGdCQp242Ikq_j1GuwKJw9PMk743hzeMveVwzaGpP55219ACR0KuuZbYo33GNlyJptQamudsAyBEqYQWV-xVSj8AQErUL9kV17WWSssN-3acrPfF5-DJrZ6KI-VlGefiMA9jOy4hFtnc-tBaX-wpUhvzckhuoGm0hZ27Yh_mJQbvqSvuaAoxDvb76IrjENzDa_aitz7Rm8vcsq-fbk77u_L-y-1hv7svnZRalspiJ52VlZCOg9IoucOq6ggkb1pLfaextlXdolPQV6Lue9c0aAUI16m-wy37cL77GMPPldJipjE58t7OFNZkqkYhqqwtwzPoYkgpUm8e4zjZ-MtwMH9qNaed-b_WnHp3Ob-2E3X_MpceM_D-AtjkrO-jnd2Y_nICKo28qTMnz9xT8AvF9ODXJ4pmIOuXweQHgcIaSwGQP5hdmSUk_gZTW5CW</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>69533553</pqid></control><display><type>article</type><title>Small Molecule Selectin Inhibitor in Global Cerebral Ischemia and Controlled Hemorrhagic Shock</title><source>MEDLINE</source><source>Journals@Ovid Complete</source><creator>Anaya-Prado, Roberto ; Pérez-Gomez, Nahum ; Toledo-Pereyra, Luis H. ; Walsh, John ; Jordan, Jackie ; Ward, Peter A.</creator><creatorcontrib>Anaya-Prado, Roberto ; Pérez-Gomez, Nahum ; Toledo-Pereyra, Luis H. ; Walsh, John ; Jordan, Jackie ; Ward, Peter A.</creatorcontrib><description>BACKGROUND:The clinical and experimental management of stroke has not reached the therapeutic success seen in other medical conditions associated with ischemia/reperfusion. In this work, we investigated the effect of a small molecule selectin inhibitor TBC-1269, in animals subjected to global cerebral ischemia (GCI) and controlled hemorrhagic shock (CHS).
METHODS:Forty-eight male Sprague-Dawley rats weighting between 275 g and 300 g were subjected to a model of GCI and CHS. Three groups of animals were included in this study (n = 16 per group)sham/saline (group 1); GCI/CHS/Saline (group 2); GCI/CHS/TBC-1269 (group 3). Experimental design consisted of bilateral carotid artery occlusion for 20 minutes, and the development of CHS until a mean arterial pressure of 50 mm Hg was reached. At 20 minutes, clamps were released, and resuscitation was achieved with normal saline, and the end point was to attain a mean arterial pressure of 80 mm Hg. Treatment at the beginning of resuscitation included either normal saline (groups 1 and 2) or TBC-1269 (25 mg/kg, group 3). The following indices were evaluatedbrain tissue myeloperoxidase, average numbers of ischemic neurons, and 7-day survival.
RESULTS:Brain myeloperoxidase was decreased in animals treated with TBC-1269, although this difference was not statistically significant. Treated animals demonstrated a significant smaller amount of ischemic neurons than the controls. Survival was also improved from 40% in controls to 80% with TBC-1269 treatment. This difference was statistically significant.
CONCLUSION:The use of a small molecule selectin inhibitor, TBC-1269, had a protective effect in this model of GCI and CHS, as evidenced by decreased numbers of ischemic neurons and improved survival rates.</description><identifier>ISSN: 0022-5282</identifier><identifier>EISSN: 1529-8809</identifier><identifier>DOI: 10.1097/TA.0b013e3181843f3a</identifier><identifier>PMID: 18784584</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins, Inc</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Biological and medical sciences ; Biphenyl Compounds - therapeutic use ; Brain Ischemia - drug therapy ; Brain Ischemia - enzymology ; Brain Ischemia - pathology ; Cell Adhesion Molecules - antagonists & inhibitors ; Disease Models, Animal ; Diseases of the osteoarticular system ; Emergency and intensive cardiocirculatory care. Cardiogenic shock. Coronary intensive care ; Intensive care medicine ; Male ; Mannose - analogs & derivatives ; Mannosides - therapeutic use ; Medical sciences ; Neurology ; Neutrophil Infiltration ; Peroxidase - metabolism ; Rats ; Rats, Sprague-Dawley ; Shock, Hemorrhagic - drug therapy ; Shock, Hemorrhagic - enzymology ; Shock, Hemorrhagic - pathology ; Vascular diseases and vascular malformations of the nervous system</subject><ispartof>The Journal of trauma, injury, infection, and critical care, 2008-09, Vol.65 (3), p.678-684</ispartof><rights>2008 Lippincott Williams & Wilkins, Inc.</rights><rights>2008 INIST-CNRS</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4484-5a3d4ca4624c1058341c366de0419baefd837a67b3c50f627ffc993a202cd5fd3</citedby><cites>FETCH-LOGICAL-c4484-5a3d4ca4624c1058341c366de0419baefd837a67b3c50f627ffc993a202cd5fd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20683197$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18784584$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Anaya-Prado, Roberto</creatorcontrib><creatorcontrib>Pérez-Gomez, Nahum</creatorcontrib><creatorcontrib>Toledo-Pereyra, Luis H.</creatorcontrib><creatorcontrib>Walsh, John</creatorcontrib><creatorcontrib>Jordan, Jackie</creatorcontrib><creatorcontrib>Ward, Peter A.</creatorcontrib><title>Small Molecule Selectin Inhibitor in Global Cerebral Ischemia and Controlled Hemorrhagic Shock</title><title>The Journal of trauma, injury, infection, and critical care</title><addtitle>J Trauma</addtitle><description>BACKGROUND:The clinical and experimental management of stroke has not reached the therapeutic success seen in other medical conditions associated with ischemia/reperfusion. In this work, we investigated the effect of a small molecule selectin inhibitor TBC-1269, in animals subjected to global cerebral ischemia (GCI) and controlled hemorrhagic shock (CHS).
METHODS:Forty-eight male Sprague-Dawley rats weighting between 275 g and 300 g were subjected to a model of GCI and CHS. Three groups of animals were included in this study (n = 16 per group)sham/saline (group 1); GCI/CHS/Saline (group 2); GCI/CHS/TBC-1269 (group 3). Experimental design consisted of bilateral carotid artery occlusion for 20 minutes, and the development of CHS until a mean arterial pressure of 50 mm Hg was reached. At 20 minutes, clamps were released, and resuscitation was achieved with normal saline, and the end point was to attain a mean arterial pressure of 80 mm Hg. Treatment at the beginning of resuscitation included either normal saline (groups 1 and 2) or TBC-1269 (25 mg/kg, group 3). The following indices were evaluatedbrain tissue myeloperoxidase, average numbers of ischemic neurons, and 7-day survival.
RESULTS:Brain myeloperoxidase was decreased in animals treated with TBC-1269, although this difference was not statistically significant. Treated animals demonstrated a significant smaller amount of ischemic neurons than the controls. Survival was also improved from 40% in controls to 80% with TBC-1269 treatment. This difference was statistically significant.
CONCLUSION:The use of a small molecule selectin inhibitor, TBC-1269, had a protective effect in this model of GCI and CHS, as evidenced by decreased numbers of ischemic neurons and improved survival rates.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biphenyl Compounds - therapeutic use</subject><subject>Brain Ischemia - drug therapy</subject><subject>Brain Ischemia - enzymology</subject><subject>Brain Ischemia - pathology</subject><subject>Cell Adhesion Molecules - antagonists & inhibitors</subject><subject>Disease Models, Animal</subject><subject>Diseases of the osteoarticular system</subject><subject>Emergency and intensive cardiocirculatory care. Cardiogenic shock. Coronary intensive care</subject><subject>Intensive care medicine</subject><subject>Male</subject><subject>Mannose - analogs & derivatives</subject><subject>Mannosides - therapeutic use</subject><subject>Medical sciences</subject><subject>Neurology</subject><subject>Neutrophil Infiltration</subject><subject>Peroxidase - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Shock, Hemorrhagic - drug therapy</subject><subject>Shock, Hemorrhagic - enzymology</subject><subject>Shock, Hemorrhagic - pathology</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><issn>0022-5282</issn><issn>1529-8809</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkUFv1DAQhS0EosvCL0BCucAtZeyxE-e4WpV2pSIOu1yxHGdCQp242Ikq_j1GuwKJw9PMk743hzeMveVwzaGpP55219ACR0KuuZbYo33GNlyJptQamudsAyBEqYQWV-xVSj8AQErUL9kV17WWSssN-3acrPfF5-DJrZ6KI-VlGefiMA9jOy4hFtnc-tBaX-wpUhvzckhuoGm0hZ27Yh_mJQbvqSvuaAoxDvb76IrjENzDa_aitz7Rm8vcsq-fbk77u_L-y-1hv7svnZRalspiJ52VlZCOg9IoucOq6ggkb1pLfaextlXdolPQV6Lue9c0aAUI16m-wy37cL77GMPPldJipjE58t7OFNZkqkYhqqwtwzPoYkgpUm8e4zjZ-MtwMH9qNaed-b_WnHp3Ob-2E3X_MpceM_D-AtjkrO-jnd2Y_nICKo28qTMnz9xT8AvF9ODXJ4pmIOuXweQHgcIaSwGQP5hdmSUk_gZTW5CW</recordid><startdate>200809</startdate><enddate>200809</enddate><creator>Anaya-Prado, Roberto</creator><creator>Pérez-Gomez, Nahum</creator><creator>Toledo-Pereyra, Luis H.</creator><creator>Walsh, John</creator><creator>Jordan, Jackie</creator><creator>Ward, Peter A.</creator><general>Lippincott Williams & Wilkins, Inc</general><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><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></search><sort><creationdate>200809</creationdate><title>Small Molecule Selectin Inhibitor in Global Cerebral Ischemia and Controlled Hemorrhagic Shock</title><author>Anaya-Prado, Roberto ; Pérez-Gomez, Nahum ; Toledo-Pereyra, Luis H. ; Walsh, John ; Jordan, Jackie ; Ward, Peter A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4484-5a3d4ca4624c1058341c366de0419baefd837a67b3c50f627ffc993a202cd5fd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biphenyl Compounds - therapeutic use</topic><topic>Brain Ischemia - drug therapy</topic><topic>Brain Ischemia - enzymology</topic><topic>Brain Ischemia - pathology</topic><topic>Cell Adhesion Molecules - antagonists & inhibitors</topic><topic>Disease Models, Animal</topic><topic>Diseases of the osteoarticular system</topic><topic>Emergency and intensive cardiocirculatory care. Cardiogenic shock. Coronary intensive care</topic><topic>Intensive care medicine</topic><topic>Male</topic><topic>Mannose - analogs & derivatives</topic><topic>Mannosides - therapeutic use</topic><topic>Medical sciences</topic><topic>Neurology</topic><topic>Neutrophil Infiltration</topic><topic>Peroxidase - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Shock, Hemorrhagic - drug therapy</topic><topic>Shock, Hemorrhagic - enzymology</topic><topic>Shock, Hemorrhagic - pathology</topic><topic>Vascular diseases and vascular malformations of the nervous system</topic><toplevel>online_resources</toplevel><creatorcontrib>Anaya-Prado, Roberto</creatorcontrib><creatorcontrib>Pérez-Gomez, Nahum</creatorcontrib><creatorcontrib>Toledo-Pereyra, Luis H.</creatorcontrib><creatorcontrib>Walsh, John</creatorcontrib><creatorcontrib>Jordan, Jackie</creatorcontrib><creatorcontrib>Ward, Peter A.</creatorcontrib><collection>Pascal-Francis</collection><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 trauma, injury, infection, and critical care</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Anaya-Prado, Roberto</au><au>Pérez-Gomez, Nahum</au><au>Toledo-Pereyra, Luis H.</au><au>Walsh, John</au><au>Jordan, Jackie</au><au>Ward, Peter A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Small Molecule Selectin Inhibitor in Global Cerebral Ischemia and Controlled Hemorrhagic Shock</atitle><jtitle>The Journal of trauma, injury, infection, and critical care</jtitle><addtitle>J Trauma</addtitle><date>2008-09</date><risdate>2008</risdate><volume>65</volume><issue>3</issue><spage>678</spage><epage>684</epage><pages>678-684</pages><issn>0022-5282</issn><eissn>1529-8809</eissn><abstract>BACKGROUND:The clinical and experimental management of stroke has not reached the therapeutic success seen in other medical conditions associated with ischemia/reperfusion. In this work, we investigated the effect of a small molecule selectin inhibitor TBC-1269, in animals subjected to global cerebral ischemia (GCI) and controlled hemorrhagic shock (CHS).
METHODS:Forty-eight male Sprague-Dawley rats weighting between 275 g and 300 g were subjected to a model of GCI and CHS. Three groups of animals were included in this study (n = 16 per group)sham/saline (group 1); GCI/CHS/Saline (group 2); GCI/CHS/TBC-1269 (group 3). Experimental design consisted of bilateral carotid artery occlusion for 20 minutes, and the development of CHS until a mean arterial pressure of 50 mm Hg was reached. At 20 minutes, clamps were released, and resuscitation was achieved with normal saline, and the end point was to attain a mean arterial pressure of 80 mm Hg. Treatment at the beginning of resuscitation included either normal saline (groups 1 and 2) or TBC-1269 (25 mg/kg, group 3). The following indices were evaluatedbrain tissue myeloperoxidase, average numbers of ischemic neurons, and 7-day survival.
RESULTS:Brain myeloperoxidase was decreased in animals treated with TBC-1269, although this difference was not statistically significant. Treated animals demonstrated a significant smaller amount of ischemic neurons than the controls. Survival was also improved from 40% in controls to 80% with TBC-1269 treatment. This difference was statistically significant.
CONCLUSION:The use of a small molecule selectin inhibitor, TBC-1269, had a protective effect in this model of GCI and CHS, as evidenced by decreased numbers of ischemic neurons and improved survival rates.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins, Inc</pub><pmid>18784584</pmid><doi>10.1097/TA.0b013e3181843f3a</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-5282 |
| ispartof | The Journal of trauma, injury, infection, and critical care, 2008-09, Vol.65 (3), p.678-684 |
| issn | 0022-5282 1529-8809 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_69533553 |
| source | MEDLINE; Journals@Ovid Complete |
| subjects | Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Biological and medical sciences Biphenyl Compounds - therapeutic use Brain Ischemia - drug therapy Brain Ischemia - enzymology Brain Ischemia - pathology Cell Adhesion Molecules - antagonists & inhibitors Disease Models, Animal Diseases of the osteoarticular system Emergency and intensive cardiocirculatory care. Cardiogenic shock. Coronary intensive care Intensive care medicine Male Mannose - analogs & derivatives Mannosides - therapeutic use Medical sciences Neurology Neutrophil Infiltration Peroxidase - metabolism Rats Rats, Sprague-Dawley Shock, Hemorrhagic - drug therapy Shock, Hemorrhagic - enzymology Shock, Hemorrhagic - pathology Vascular diseases and vascular malformations of the nervous system |
| title | Small Molecule Selectin Inhibitor in Global Cerebral Ischemia and Controlled Hemorrhagic Shock |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T08%3A10%3A32IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Small%20Molecule%20Selectin%20Inhibitor%20in%20Global%20Cerebral%20Ischemia%20and%20Controlled%20Hemorrhagic%20Shock&rft.jtitle=The%20Journal%20of%20trauma,%20injury,%20infection,%20and%20critical%20care&rft.au=Anaya-Prado,%20Roberto&rft.date=2008-09&rft.volume=65&rft.issue=3&rft.spage=678&rft.epage=684&rft.pages=678-684&rft.issn=0022-5282&rft.eissn=1529-8809&rft_id=info:doi/10.1097/TA.0b013e3181843f3a&rft_dat=%3Cproquest_cross%3E69533553%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=69533553&rft_id=info:pmid/18784584&rfr_iscdi=true |