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.

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. Research Abstract Details 

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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. Abstract Text:

Anna Rosell,Eloy Cuadrado,Arantxa Ortega-Aznar,Mar ,Eng H Lo,Joan Montaner,Anna Rosell,Eloy Cuadrado,Arantxa Ortega-Aznar,Mar ,Eng H Lo,Joan Montaner,

BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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. Publishing Authors By Initials

A Rosell,E Cuadrado,A Ortega-Aznar,M ,EH Lo,J Montaner,A Rosell,E Cuadrado,A Ortega-Aznar,M ,EH Lo,J Montaner,

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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. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Stroke; a journal of cerebral circulation

VOLUME: 39

Page Numbers: 1121-6

Journal Abbreviation: Stroke

ISSN: 1524-4628

DAY: 6

MONTH: 03

YEAR: 2008

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. Information

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LANGUAGE: eng

NlmUniqueID: 235266

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AFFILIATION: Neurovascular Research Laboratory, Neurovascular Unit, Department of Neurology, Universitat Autònoma de Barcelona, Institut de Recerca, Hospital Vall d'Hebron, Barcelona, Spain.

Country: United States

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MEDLINETA: Stroke

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