MMP-9-Positive Neutrophil Infiltration Is Associated to Blood-Brain Barrier Breakdown and Basal Lamina Type IV Collagen Degradation During Hemorrhagic Transformation After Human Ischemic Stroke
An abnormal expression of some matrix metalloproteinases (MMPs) is related with hemorrhagic transformation events after stroke. Our aim was to investigate MMP-2 and MMP-9 in the ischemic brain and its relation with blood-brain barrier breakdown after hemorrhagic transformation in human stroke. We as...
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| Veröffentlicht in: | Stroke (1970) 2008-04, Vol.39 (4), p.1121-1126 |
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| container_title | Stroke (1970) |
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| creator | ROSELL, Anna CUADRADO, Eloy ORTEGA-AZNAR, Arantxa HERNANDEZ-GUILLAMON, Mar LO, Eng H MONTANER, Joan |
| description | An abnormal expression of some matrix metalloproteinases (MMPs) is related with hemorrhagic transformation events after stroke. Our aim was to investigate MMP-2 and MMP-9 in the ischemic brain and its relation with blood-brain barrier breakdown after hemorrhagic transformation in human stroke.
We assessed 5 cases of fatal ischemic strokes with hemorrhagic complications; brain samples were obtained from infarct, hemorrhagic, and contralateral tissue. MMP-9 and MMP-2 content was analyzed by zymography and immunohistochemistry was performed to localize MMP-9 and to assess collagen IV integrity in the basal lamina. Laser capture microdissection was performed to isolate blood-brain barrier vessels to study these MMPs.
Overall, MMP-9 levels were higher both in hemorrhagic and nonhemorrhagic infarcted tissue compared to contralateral areas (P |
| doi_str_mv | 10.1161/strokeaha.107.500868 |
| format | Article |
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We assessed 5 cases of fatal ischemic strokes with hemorrhagic complications; brain samples were obtained from infarct, hemorrhagic, and contralateral tissue. MMP-9 and MMP-2 content was analyzed by zymography and immunohistochemistry was performed to localize MMP-9 and to assess collagen IV integrity in the basal lamina. Laser capture microdissection was performed to isolate blood-brain barrier vessels to study these MMPs.
Overall, MMP-9 levels were higher both in hemorrhagic and nonhemorrhagic infarcted tissue compared to contralateral areas (P<0.0001 and P<0.05). Moreover, levels of the cleaved MMP-9 85kDa-form were significantly elevated in the hemorrhagic compared to nonhemorrhagic and contralateral areas (P=0.033 and P<0.0001). No changes were found for MMP-2 content. Immunostaining revealed a strong MMP-9-positive neutrophil infiltration surrounding brain microvessels associated with severe basal lamina type IV collagen degradation and blood extravasation. Microdissection confirmed that content of MMP-9 was similarly high in microvessel endothelium from hemorrhagic and infarcted areas compared to contralateral hemisphere vessels (P<0.05), pointing to neutrophils surrounding dissected microvessels as the main source of MMP-9 in hemorrhagic areas.
Our results show a strong neutrophil infiltration in the infarcted and hemorrhagic areas with local high MMP-9 content closely related to basal lamina collagen IV degradation and blood-brain barrier breakdown. Microvessel and inflammatory MMP-9 response are associated with hemorrhagic complications after stroke.</description><identifier>ISSN: 0039-2499</identifier><identifier>EISSN: 1524-4628</identifier><identifier>DOI: 10.1161/strokeaha.107.500868</identifier><identifier>PMID: 18323498</identifier><identifier>CODEN: SJCCA7</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Basement Membrane - enzymology ; Basement Membrane - immunology ; Basement Membrane - pathology ; Biological and medical sciences ; Blood-Brain Barrier - enzymology ; Blood-Brain Barrier - immunology ; Blood-Brain Barrier - pathology ; Brain - enzymology ; Brain - immunology ; Brain - pathology ; Brain Ischemia - immunology ; Brain Ischemia - metabolism ; Brain Ischemia - pathology ; Cerebral Hemorrhage - immunology ; Cerebral Hemorrhage - metabolism ; Cerebral Hemorrhage - pathology ; Collagen Type IV - metabolism ; Endothelium, Vascular - enzymology ; Endothelium, Vascular - immunology ; Endothelium, Vascular - pathology ; Female ; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy ; Humans ; Immunohistochemistry ; Male ; Matrix Metalloproteinase 2 - metabolism ; Matrix Metalloproteinase 9 - metabolism ; Medical sciences ; Nervous system (semeiology, syndromes) ; Neurology ; Neutrophils - pathology ; Stroke - immunology ; Stroke - metabolism ; Stroke - pathology ; Vascular diseases and vascular malformations of the nervous system</subject><ispartof>Stroke (1970), 2008-04, Vol.39 (4), p.1121-1126</ispartof><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c565t-b7f96d5ab89417a77dc1ac18f64c78543fd53fc4ff0c4d5032d12034ab56d9893</citedby><cites>FETCH-LOGICAL-c565t-b7f96d5ab89417a77dc1ac18f64c78543fd53fc4ff0c4d5032d12034ab56d9893</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3685,27922,27923</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20214809$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18323498$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ROSELL, Anna</creatorcontrib><creatorcontrib>CUADRADO, Eloy</creatorcontrib><creatorcontrib>ORTEGA-AZNAR, Arantxa</creatorcontrib><creatorcontrib>HERNANDEZ-GUILLAMON, Mar</creatorcontrib><creatorcontrib>LO, Eng H</creatorcontrib><creatorcontrib>MONTANER, Joan</creatorcontrib><title>MMP-9-Positive Neutrophil Infiltration Is Associated to Blood-Brain Barrier Breakdown and Basal Lamina Type IV Collagen Degradation During Hemorrhagic Transformation After Human Ischemic Stroke</title><title>Stroke (1970)</title><addtitle>Stroke</addtitle><description>An abnormal expression of some matrix metalloproteinases (MMPs) is related with hemorrhagic transformation events after stroke. Our aim was to investigate MMP-2 and MMP-9 in the ischemic brain and its relation with blood-brain barrier breakdown after hemorrhagic transformation in human stroke.
We assessed 5 cases of fatal ischemic strokes with hemorrhagic complications; brain samples were obtained from infarct, hemorrhagic, and contralateral tissue. MMP-9 and MMP-2 content was analyzed by zymography and immunohistochemistry was performed to localize MMP-9 and to assess collagen IV integrity in the basal lamina. Laser capture microdissection was performed to isolate blood-brain barrier vessels to study these MMPs.
Overall, MMP-9 levels were higher both in hemorrhagic and nonhemorrhagic infarcted tissue compared to contralateral areas (P<0.0001 and P<0.05). Moreover, levels of the cleaved MMP-9 85kDa-form were significantly elevated in the hemorrhagic compared to nonhemorrhagic and contralateral areas (P=0.033 and P<0.0001). No changes were found for MMP-2 content. Immunostaining revealed a strong MMP-9-positive neutrophil infiltration surrounding brain microvessels associated with severe basal lamina type IV collagen degradation and blood extravasation. Microdissection confirmed that content of MMP-9 was similarly high in microvessel endothelium from hemorrhagic and infarcted areas compared to contralateral hemisphere vessels (P<0.05), pointing to neutrophils surrounding dissected microvessels as the main source of MMP-9 in hemorrhagic areas.
Our results show a strong neutrophil infiltration in the infarcted and hemorrhagic areas with local high MMP-9 content closely related to basal lamina collagen IV degradation and blood-brain barrier breakdown. Microvessel and inflammatory MMP-9 response are associated with hemorrhagic complications after stroke.</description><subject>Basement Membrane - enzymology</subject><subject>Basement Membrane - immunology</subject><subject>Basement Membrane - pathology</subject><subject>Biological and medical sciences</subject><subject>Blood-Brain Barrier - enzymology</subject><subject>Blood-Brain Barrier - immunology</subject><subject>Blood-Brain Barrier - pathology</subject><subject>Brain - enzymology</subject><subject>Brain - immunology</subject><subject>Brain - pathology</subject><subject>Brain Ischemia - immunology</subject><subject>Brain Ischemia - metabolism</subject><subject>Brain Ischemia - pathology</subject><subject>Cerebral Hemorrhage - immunology</subject><subject>Cerebral Hemorrhage - metabolism</subject><subject>Cerebral Hemorrhage - pathology</subject><subject>Collagen Type IV - metabolism</subject><subject>Endothelium, Vascular - enzymology</subject><subject>Endothelium, Vascular - immunology</subject><subject>Endothelium, Vascular - pathology</subject><subject>Female</subject><subject>Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Matrix Metalloproteinase 9 - metabolism</subject><subject>Medical sciences</subject><subject>Nervous system (semeiology, syndromes)</subject><subject>Neurology</subject><subject>Neutrophils - pathology</subject><subject>Stroke - immunology</subject><subject>Stroke - metabolism</subject><subject>Stroke - pathology</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><issn>0039-2499</issn><issn>1524-4628</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc-O0zAQhy0EYsvCGyDkC9xS7NhO7GPaXWhFl12xhWs09Z_WbBJ37QS0j8ebkSUVHDmNNPrm08z8EHpNyZzSgr5PfQx3Fg4wp6ScC0JkIZ-gGRU5z3iRy6doRghTWc6VOkMvUvpOCMmZFM_RGZUsZ1zJGfp1dXWTqewmJN_7HxZ_tsPoPR58g9ed800fofehw-uEq5SC9tBbg_uAF00IJltE8B1eQIzeRryIFu5M-Nlh6MzYTdDgDbS-A7x9OFq8_oaXoWlgbzt8YfcRzCS_GKLv9nhl2xDjAfZe422ELrkQ24moXD_6V0MLj6vog21H5vbPB16iZw6aZF-d6jn6-uFyu1xlm-uP62W1ybQoRJ_tSqcKI2AnFacllKXRFDSVruC6lIIzZwRzmjtHNDeCsNzQnDAOO1EYJRU7R-8m7zGG-8Gmvm590nY8p7NhSHVJOGOM8v-COSmE4lKOIJ9AHUNK0br6GH0L8aGmpH7MuL7dfrn-dFmtqrFT1lPG49ibk3_Ytdb8GzqFOgJvTwAkDY0bX6l9-svlJKdcEsV-A6b4s-I</recordid><startdate>20080401</startdate><enddate>20080401</enddate><creator>ROSELL, Anna</creator><creator>CUADRADO, Eloy</creator><creator>ORTEGA-AZNAR, Arantxa</creator><creator>HERNANDEZ-GUILLAMON, Mar</creator><creator>LO, Eng H</creator><creator>MONTANER, Joan</creator><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>7TK</scope><scope>7X8</scope></search><sort><creationdate>20080401</creationdate><title>MMP-9-Positive Neutrophil Infiltration Is Associated to Blood-Brain Barrier Breakdown and Basal Lamina Type IV Collagen Degradation During Hemorrhagic Transformation After Human Ischemic Stroke</title><author>ROSELL, Anna ; CUADRADO, Eloy ; ORTEGA-AZNAR, Arantxa ; HERNANDEZ-GUILLAMON, Mar ; LO, Eng H ; MONTANER, Joan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c565t-b7f96d5ab89417a77dc1ac18f64c78543fd53fc4ff0c4d5032d12034ab56d9893</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Basement Membrane - enzymology</topic><topic>Basement Membrane - immunology</topic><topic>Basement Membrane - pathology</topic><topic>Biological and medical sciences</topic><topic>Blood-Brain Barrier - enzymology</topic><topic>Blood-Brain Barrier - immunology</topic><topic>Blood-Brain Barrier - pathology</topic><topic>Brain - enzymology</topic><topic>Brain - immunology</topic><topic>Brain - pathology</topic><topic>Brain Ischemia - immunology</topic><topic>Brain Ischemia - metabolism</topic><topic>Brain Ischemia - pathology</topic><topic>Cerebral Hemorrhage - immunology</topic><topic>Cerebral Hemorrhage - metabolism</topic><topic>Cerebral Hemorrhage - pathology</topic><topic>Collagen Type IV - metabolism</topic><topic>Endothelium, Vascular - enzymology</topic><topic>Endothelium, Vascular - immunology</topic><topic>Endothelium, Vascular - pathology</topic><topic>Female</topic><topic>Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Matrix Metalloproteinase 2 - metabolism</topic><topic>Matrix Metalloproteinase 9 - metabolism</topic><topic>Medical sciences</topic><topic>Nervous system (semeiology, syndromes)</topic><topic>Neurology</topic><topic>Neutrophils - pathology</topic><topic>Stroke - immunology</topic><topic>Stroke - metabolism</topic><topic>Stroke - pathology</topic><topic>Vascular diseases and vascular malformations of the nervous system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ROSELL, Anna</creatorcontrib><creatorcontrib>CUADRADO, Eloy</creatorcontrib><creatorcontrib>ORTEGA-AZNAR, Arantxa</creatorcontrib><creatorcontrib>HERNANDEZ-GUILLAMON, Mar</creatorcontrib><creatorcontrib>LO, Eng H</creatorcontrib><creatorcontrib>MONTANER, Joan</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>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Stroke (1970)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ROSELL, Anna</au><au>CUADRADO, Eloy</au><au>ORTEGA-AZNAR, Arantxa</au><au>HERNANDEZ-GUILLAMON, Mar</au><au>LO, Eng H</au><au>MONTANER, Joan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MMP-9-Positive Neutrophil Infiltration Is Associated to Blood-Brain Barrier Breakdown and Basal Lamina Type IV Collagen Degradation During Hemorrhagic Transformation After Human Ischemic Stroke</atitle><jtitle>Stroke (1970)</jtitle><addtitle>Stroke</addtitle><date>2008-04-01</date><risdate>2008</risdate><volume>39</volume><issue>4</issue><spage>1121</spage><epage>1126</epage><pages>1121-1126</pages><issn>0039-2499</issn><eissn>1524-4628</eissn><coden>SJCCA7</coden><abstract>An abnormal expression of some matrix metalloproteinases (MMPs) is related with hemorrhagic transformation events after stroke. Our aim was to investigate MMP-2 and MMP-9 in the ischemic brain and its relation with blood-brain barrier breakdown after hemorrhagic transformation in human stroke.
We assessed 5 cases of fatal ischemic strokes with hemorrhagic complications; brain samples were obtained from infarct, hemorrhagic, and contralateral tissue. MMP-9 and MMP-2 content was analyzed by zymography and immunohistochemistry was performed to localize MMP-9 and to assess collagen IV integrity in the basal lamina. Laser capture microdissection was performed to isolate blood-brain barrier vessels to study these MMPs.
Overall, MMP-9 levels were higher both in hemorrhagic and nonhemorrhagic infarcted tissue compared to contralateral areas (P<0.0001 and P<0.05). Moreover, levels of the cleaved MMP-9 85kDa-form were significantly elevated in the hemorrhagic compared to nonhemorrhagic and contralateral areas (P=0.033 and P<0.0001). No changes were found for MMP-2 content. Immunostaining revealed a strong MMP-9-positive neutrophil infiltration surrounding brain microvessels associated with severe basal lamina type IV collagen degradation and blood extravasation. Microdissection confirmed that content of MMP-9 was similarly high in microvessel endothelium from hemorrhagic and infarcted areas compared to contralateral hemisphere vessels (P<0.05), pointing to neutrophils surrounding dissected microvessels as the main source of MMP-9 in hemorrhagic areas.
Our results show a strong neutrophil infiltration in the infarcted and hemorrhagic areas with local high MMP-9 content closely related to basal lamina collagen IV degradation and blood-brain barrier breakdown. Microvessel and inflammatory MMP-9 response are associated with hemorrhagic complications after stroke.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>18323498</pmid><doi>10.1161/strokeaha.107.500868</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Stroke (1970), 2008-04, Vol.39 (4), p.1121-1126 |
| issn | 0039-2499 1524-4628 |
| language | eng |
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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 | Basement Membrane - enzymology Basement Membrane - immunology Basement Membrane - pathology Biological and medical sciences Blood-Brain Barrier - enzymology Blood-Brain Barrier - immunology Blood-Brain Barrier - pathology Brain - enzymology Brain - immunology Brain - pathology Brain Ischemia - immunology Brain Ischemia - metabolism Brain Ischemia - pathology Cerebral Hemorrhage - immunology Cerebral Hemorrhage - metabolism Cerebral Hemorrhage - pathology Collagen Type IV - metabolism Endothelium, Vascular - enzymology Endothelium, Vascular - immunology Endothelium, Vascular - pathology Female Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy Humans Immunohistochemistry Male Matrix Metalloproteinase 2 - metabolism Matrix Metalloproteinase 9 - metabolism Medical sciences Nervous system (semeiology, syndromes) Neurology Neutrophils - pathology Stroke - immunology Stroke - metabolism Stroke - pathology Vascular diseases and vascular malformations of the nervous system |
| title | MMP-9-Positive Neutrophil Infiltration Is Associated to Blood-Brain Barrier Breakdown and Basal Lamina Type IV Collagen Degradation During Hemorrhagic Transformation After Human Ischemic Stroke |
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