Vascular Protection in Diabetic Stroke: Role of Matrix Metalloprotease-Dependent Vascular Remodeling
Temporary focal ischemia causes greater hemorrhagic transformation (HT) in diabetic Goto-Kakizaki (GK) rats, a model with increased cerebrovascular matrix metalloprotease (MMP) activity and tortuosity. The objective of the current study was to test the hypotheses that (1) diabetes-induced cerebrovas...
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| Veröffentlicht in: | Journal of cerebral blood flow and metabolism 2010-12, Vol.30 (12), p.1928-1938 |
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| creator | Elgebaly, Mostafa M Prakash, Roshini Li, Weiguo Ogbi, Safia Johnson, Maribeth H Mezzetti, Erin M Fagan, Susan C Ergul, Adviye |
| description | Temporary focal ischemia causes greater hemorrhagic transformation (HT) in diabetic Goto-Kakizaki (GK) rats, a model with increased cerebrovascular matrix metalloprotease (MMP) activity and tortuosity. The objective of the current study was to test the hypotheses that (1) diabetes-induced cerebrovascular remodeling is MMP dependent and (2) prevention of vascular remodeling by glucose control or MMP inhibition reduces HT in diabetic stroke. Control and GK rats were treated with vehicle, metformin, or minocycline for 4 weeks, and indices of remodeling including vascular tortuosity index, lumen diameter, number of collaterals, and middle cerebral artery (MCA) MMP activity were measured. Additional animals were subjected to 3 hours MCA occlusion/21 hours reperfusion, and infarct size and HT were evaluated as indices of neurovascular injury. All remodeling markers including MMP-9 activity were increased in diabetes. Infarct size was smaller in minocycline-treated animals. Both metformin and minocycline reduced vascular remodeling and severity of HT in diabetes. These results provide evidence that diabetes-mediated stimulation of MMP-9 activity promotes cerebrovascular remodeling, which contributes to greater HT in diabetes. Metformin and minocycline offer vascular protection, which has important clinical implications for diabetes patients who are at a fourfold to sixfold higher risk for stroke. |
| doi_str_mv | 10.1038/jcbfm.2010.120 |
| format | Article |
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The objective of the current study was to test the hypotheses that (1) diabetes-induced cerebrovascular remodeling is MMP dependent and (2) prevention of vascular remodeling by glucose control or MMP inhibition reduces HT in diabetic stroke. Control and GK rats were treated with vehicle, metformin, or minocycline for 4 weeks, and indices of remodeling including vascular tortuosity index, lumen diameter, number of collaterals, and middle cerebral artery (MCA) MMP activity were measured. Additional animals were subjected to 3 hours MCA occlusion/21 hours reperfusion, and infarct size and HT were evaluated as indices of neurovascular injury. All remodeling markers including MMP-9 activity were increased in diabetes. Infarct size was smaller in minocycline-treated animals. Both metformin and minocycline reduced vascular remodeling and severity of HT in diabetes. These results provide evidence that diabetes-mediated stimulation of MMP-9 activity promotes cerebrovascular remodeling, which contributes to greater HT in diabetes. Metformin and minocycline offer vascular protection, which has important clinical implications for diabetes patients who are at a fourfold to sixfold higher risk for stroke.</description><identifier>ISSN: 0271-678X</identifier><identifier>EISSN: 1559-7016</identifier><identifier>DOI: 10.1038/jcbfm.2010.120</identifier><identifier>PMID: 20664613</identifier><identifier>CODEN: JCBMDN</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Animals ; Biological and medical sciences ; Brain Ischemia - enzymology ; Brain Ischemia - etiology ; Diabetes Complications - enzymology ; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy ; Humans ; Male ; Matrix Metalloproteinases - metabolism ; Medical sciences ; Nervous system (semeiology, syndromes) ; Neurology ; Original ; Rats ; Vascular diseases and vascular malformations of the nervous system</subject><ispartof>Journal of cerebral blood flow and metabolism, 2010-12, Vol.30 (12), p.1928-1938</ispartof><rights>2010 ISCBFM</rights><rights>2015 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Dec 2010</rights><rights>Copyright © 2010 International Society for Cerebral Blood Flow & Metabolism, Inc. 2010 International Society for Cerebral Blood Flow & Metabolism, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c514t-2bf8d99e6f08f7b9e9703ccf7543c65ea9edbefc46b69ab08383d5618b8c4d913</citedby><cites>FETCH-LOGICAL-c514t-2bf8d99e6f08f7b9e9703ccf7543c65ea9edbefc46b69ab08383d5618b8c4d913</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/PMC3002883/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002883/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,21799,27903,27904,43600,43601,53769,53771</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23911790$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20664613$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Elgebaly, Mostafa M</creatorcontrib><creatorcontrib>Prakash, Roshini</creatorcontrib><creatorcontrib>Li, Weiguo</creatorcontrib><creatorcontrib>Ogbi, Safia</creatorcontrib><creatorcontrib>Johnson, Maribeth H</creatorcontrib><creatorcontrib>Mezzetti, Erin M</creatorcontrib><creatorcontrib>Fagan, Susan C</creatorcontrib><creatorcontrib>Ergul, Adviye</creatorcontrib><title>Vascular Protection in Diabetic Stroke: Role of Matrix Metalloprotease-Dependent Vascular Remodeling</title><title>Journal of cerebral blood flow and metabolism</title><addtitle>J Cereb Blood Flow Metab</addtitle><description>Temporary focal ischemia causes greater hemorrhagic transformation (HT) in diabetic Goto-Kakizaki (GK) rats, a model with increased cerebrovascular matrix metalloprotease (MMP) activity and tortuosity. The objective of the current study was to test the hypotheses that (1) diabetes-induced cerebrovascular remodeling is MMP dependent and (2) prevention of vascular remodeling by glucose control or MMP inhibition reduces HT in diabetic stroke. Control and GK rats were treated with vehicle, metformin, or minocycline for 4 weeks, and indices of remodeling including vascular tortuosity index, lumen diameter, number of collaterals, and middle cerebral artery (MCA) MMP activity were measured. Additional animals were subjected to 3 hours MCA occlusion/21 hours reperfusion, and infarct size and HT were evaluated as indices of neurovascular injury. All remodeling markers including MMP-9 activity were increased in diabetes. Infarct size was smaller in minocycline-treated animals. Both metformin and minocycline reduced vascular remodeling and severity of HT in diabetes. 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Cerebral palsy</subject><subject>Humans</subject><subject>Male</subject><subject>Matrix Metalloproteinases - metabolism</subject><subject>Medical sciences</subject><subject>Nervous system (semeiology, syndromes)</subject><subject>Neurology</subject><subject>Original</subject><subject>Rats</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><issn>0271-678X</issn><issn>1559-7016</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</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><recordid>eNqFkV1rFDEUhoModq3eeimDIF7IrMlkkkl6IUjrR6FFqR94FzKZkzVrZrImM2L_fTPudquCeBVCnvPmnPMg9JDgJcFUPF-b1vbLCs_3Ct9CC8KYLBtM-G20wFVDSt6ILwfoXkprjLGgjN1FBxXmvOaELlD3WSczeR2L9zGMYEYXhsINxYnTLYzOFB_GGL7BUXERPBTBFud6jO5ncQ6j9j5s5iKdoDyBDQwdDGOxD7yAPnTg3bC6j-5Y7RM82J2H6NPrVx-P35Zn796cHr88Kw0j9VhWrRWdlMAtFrZpJcgGU2Nsw2pqOAMtoWvBmpq3XOo2DyNoxzgRrTB1Jwk9RC-2uZup7aEzuZ2ovdpE1-t4qYJ26s-XwX1Vq_BDUYwrIWgOeLoLiOH7BGlUvUsGvNcDhCkpyWqORUXJf0mRPbAa1zyTj_8i12GKQ97DDFHCa9lkaLmFTAwpRbD7pglWs2j1S7SaRassOhc8-n3UPX5tNgNPdkD2ob2NejAu3XBUEtLIOejZlkt6BTet_ePbK-u9wS4</recordid><startdate>20101201</startdate><enddate>20101201</enddate><creator>Elgebaly, Mostafa M</creator><creator>Prakash, Roshini</creator><creator>Li, Weiguo</creator><creator>Ogbi, Safia</creator><creator>Johnson, Maribeth H</creator><creator>Mezzetti, Erin M</creator><creator>Fagan, Susan C</creator><creator>Ergul, Adviye</creator><general>SAGE Publications</general><general>Nature Publishing Group</general><general>Sage Publications Ltd</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7TK</scope><scope>5PM</scope></search><sort><creationdate>20101201</creationdate><title>Vascular Protection in Diabetic Stroke: Role of Matrix Metalloprotease-Dependent Vascular Remodeling</title><author>Elgebaly, Mostafa M ; Prakash, Roshini ; Li, Weiguo ; Ogbi, Safia ; Johnson, Maribeth H ; Mezzetti, Erin M ; Fagan, Susan C ; Ergul, Adviye</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c514t-2bf8d99e6f08f7b9e9703ccf7543c65ea9edbefc46b69ab08383d5618b8c4d913</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Brain Ischemia - enzymology</topic><topic>Brain Ischemia - etiology</topic><topic>Diabetes Complications - enzymology</topic><topic>Headache. 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| subjects | Animals Biological and medical sciences Brain Ischemia - enzymology Brain Ischemia - etiology Diabetes Complications - enzymology Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy Humans Male Matrix Metalloproteinases - metabolism Medical sciences Nervous system (semeiology, syndromes) Neurology Original Rats Vascular diseases and vascular malformations of the nervous system |
| title | Vascular Protection in Diabetic Stroke: Role of Matrix Metalloprotease-Dependent Vascular Remodeling |
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