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We previously showed MMP-9 in the extracellular space of brain parenchyma along with neutrophil recruitment after ischemia. In the present study, we tested whether neutrophils were a direct source of enhanced MMP-9 in the ischemic brain. Neutrophil infiltration was prevented either by injecting an antibody against ICAM-1, which abrogates neutrophil adhesion to the endothelial vessel wall, or by inducing neutropenia. Onehour intraluminal middle cerebral artery occlusion with reperfusion was induced, and studies were performed at 24 hours. Circulating neutrophils expressed 95-kDa MMP-9 and dimers, and infiltrated neutrophils stained positive for MMP-9. The expression of MMP-9 (mainly 95-kDa proform and dimers and, to a lesser extent, 88-kDa form) increased in brain after ischemia/reperfusion. Treatments preventing neutrophil infiltration failed to preclude the ischemia-induced increase in 88-kDa MMP-9 form and gelatinase activity in neurons and blood vessels. However, these treatments prevented the major increase in 95-kDa MMP-9 form and dimers. We conclude that neutrophil infiltration highly contributes to enhanced MMP-9 in the ischemic brain by releasing MMP-9 proform, which might participate in the tissular inflammatory reaction.","publication_date":"2003,,","publication_name":"Journal of Cerebral Blood Flow \u0026 Metabolism","grobid_abstract_attachment_id":"40358259"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"Neutrophil Infiltration Increases Matrix Metalloproteinase-9 in the Ischemic Brain after Occlusion/Reperfusion of the Middle Cerebral Artery in Rats","broadcastable":false,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [39114025]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "full_page_mobile_sutd_modal"; window.loswp.useOptimizedScribd4genScript = false; 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src="//a.academia-assets.com/images/s65_no_pic.png" />Ramón Deulofeu</a></div><p class="ds-work-card--detail ds2-5-body-sm">2003, Journal of Cerebral Blood Flow & Metabolism</p><div class="ds-work-card--button-container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--work-card","attachmentId":40358259,"attachmentType":"pdf","workUrl":"https://www.academia.edu/18969719/Neutrophil_Infiltration_Increases_Matrix_Metalloproteinase_9_in_the_Ischemic_Brain_after_Occlusion_Reperfusion_of_the_Middle_Cerebral_Artery_in_Rats"}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--work-card","attachmentId":40358259,"attachmentType":"pdf","workUrl":"https://www.academia.edu/18969719/Neutrophil_Infiltration_Increases_Matrix_Metalloproteinase_9_in_the_Ischemic_Brain_after_Occlusion_Reperfusion_of_the_Middle_Cerebral_Artery_in_Rats"}"><span 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href="https://www.academia.edu/102861934/Leukocyte_derived_matrix_metalloproteinase_9_mediates_blood_brain_barrier_breakdown_and_is_proinflammatory_after_transient_focal_cerebral_ischemia">Leukocyte-derived matrix metalloproteinase-9 mediates blood-brain barrier breakdown and is proinflammatory after transient focal cerebral ischemia</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="272466773" href="https://independent.academia.edu/RonaldoAguilarperez">Ronaldo Aguilar perez</a></div><p class="ds-related-work--metadata ds2-5-body-xs">American Journal of Physiology-Heart and Circulatory Physiology, 2005</p><p class="ds-related-work--abstract ds2-5-body-sm">Results of recent studies reveal vascular and neuroprotective effects of matrix metalloproteinase-9 (MMP-9) inhibition and MMP-9 gene deletion in experimental stroke. However, the cellular source of MMP-9 produced in the ischemic brain and the mechanistic basis of MMP-9-mediated brain injury require elucidation. In the present study, we used MMP-9−/−mice and chimeric knockouts lacking either MMP-9 in leukocytes or in resident brain cells to test the hypothesis that MMP-9 released from leukocytes recruited to the brain during postischemic reperfusion contributes to this injury phenotype. We also tested the hypothesis that MMP-9 promotes leukocyte recruitment to the ischemic brain and thus is proinflammatory. The extent of blood-brain barrier (BBB) breakdown, the neurological deficit, and the volume of infarction resulting from transient focal stroke were abrogated to a similar extent in MMP-9−/−mice and in chimeras lacking leukocytic MMP-9 but not in chimeras with MMP-9-containing le...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Leukocyte-derived matrix metalloproteinase-9 mediates blood-brain barrier breakdown and is proinflammatory after transient focal cerebral ischemia","attachmentId":103018372,"attachmentType":"pdf","work_url":"https://www.academia.edu/102861934/Leukocyte_derived_matrix_metalloproteinase_9_mediates_blood_brain_barrier_breakdown_and_is_proinflammatory_after_transient_focal_cerebral_ischemia","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/102861934/Leukocyte_derived_matrix_metalloproteinase_9_mediates_blood_brain_barrier_breakdown_and_is_proinflammatory_after_transient_focal_cerebral_ischemia"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="1" data-entity-id="17975574" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/17975574/Matrix_Metalloproteinase_Expression_Increases_After_Cerebral_Focal_Ischemia_in_Rats_Inhibition_of_Matrix_Metalloproteinase_9_Reduces_Infarct_Size_Editorial_Comment_Inhibition_of_Matrix_Metalloproteinase_9_Reduces_Infarct_Size">Matrix Metalloproteinase Expression Increases After Cerebral Focal Ischemia in Rats : Inhibition of Matrix Metalloproteinase-9 Reduces Infarct Size Editorial Comment: Inhibition of Matrix Metalloproteinase-9 Reduces Infarct Size</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="37900667" href="https://downstate.academia.edu/FrankBarone">Frank Barone</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Stroke, 1998</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Matrix Metalloproteinase Expression Increases After Cerebral Focal Ischemia in Rats : Inhibition of Matrix Metalloproteinase-9 Reduces Infarct Size Editorial Comment: Inhibition of Matrix Metalloproteinase-9 Reduces Infarct Size","attachmentId":39809049,"attachmentType":"pdf","work_url":"https://www.academia.edu/17975574/Matrix_Metalloproteinase_Expression_Increases_After_Cerebral_Focal_Ischemia_in_Rats_Inhibition_of_Matrix_Metalloproteinase_9_Reduces_Infarct_Size_Editorial_Comment_Inhibition_of_Matrix_Metalloproteinase_9_Reduces_Infarct_Size","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/17975574/Matrix_Metalloproteinase_Expression_Increases_After_Cerebral_Focal_Ischemia_in_Rats_Inhibition_of_Matrix_Metalloproteinase_9_Reduces_Infarct_Size_Editorial_Comment_Inhibition_of_Matrix_Metalloproteinase_9_Reduces_Infarct_Size"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="2" data-entity-id="88896404" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/88896404/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</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="54261352" href="https://independent.academia.edu/MarHernandezGuillamon">Mar Hernández-Guillamon</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Stroke, 2008</p><p class="ds-related-work--abstract ds2-5-body-sm">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 &lt;0.0001 and P &lt;0.05). Moreover, levels of the cleaved MMP-9 85kDa-form were significantly elevated i...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_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","attachmentId":92793217,"attachmentType":"pdf","work_url":"https://www.academia.edu/88896404/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","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/88896404/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"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="3" data-entity-id="76155363" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/76155363/Implications_of_MMP9_for_Blood_Brain_Barrier_Disruption_and_Hemorrhagic_Transformation_Following_Ischemic_Stroke">Implications of MMP9 for Blood Brain Barrier Disruption and Hemorrhagic Transformation Following Ischemic Stroke</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32675304" href="https://ucdavis.academia.edu/FrankSharp">Frank Sharp</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Frontiers in Cellular Neuroscience, 2016</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Implications of MMP9 for Blood Brain Barrier Disruption and Hemorrhagic Transformation Following Ischemic Stroke","attachmentId":84016757,"attachmentType":"pdf","work_url":"https://www.academia.edu/76155363/Implications_of_MMP9_for_Blood_Brain_Barrier_Disruption_and_Hemorrhagic_Transformation_Following_Ischemic_Stroke","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/76155363/Implications_of_MMP9_for_Blood_Brain_Barrier_Disruption_and_Hemorrhagic_Transformation_Following_Ischemic_Stroke"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="4" data-entity-id="18594797" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/18594797/Matrix_metalloproteinase_9_and_myeloperoxidase_expression_quantitative_analysis_by_antigen_immunohistochemistry_in_a_model_of_transient_focal_cerebral_ischemia">Matrix metalloproteinase-9 and myeloperoxidase expression: quantitative analysis by antigen immunohistochemistry in a model of transient focal cerebral ischemia</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="38634677" href="https://independent.academia.edu/CarolinaMaier">Carolina Maier</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Stroke; a journal of cerebral circulation, 2004</p><p class="ds-related-work--abstract ds2-5-body-sm">Expression of matrix metalloproteinases (MMPs), proteolytic enzymes that degrade extracellular proteins, is altered after ischemia/reperfusion injury and may contribute to blood-brain barrier (BBB) breakdown. Neutrophils, a source of reactive oxygen species and MMP-9, infiltrate damaged tissue 6 to 24 hours after ischemia and have also been implicated in delayed secondary tissue damage. Here we examined the spatial-temporal relation between MMP-9 expression and neutrophil infiltration after stroke. Knockout mice containing 50% manganese superoxide dismutase activity (SOD2-KOs), which are more susceptible to ischemic damage than wild-type (WT) littermates, underwent quantitative antigen (MMP-9, myeloperoxidase) immunohistochemistry (24 and 72 hours) analysis and protein expression by Western blotting (6, 12, 24, 48, and 72 hours) after transient focal cerebral ischemia. BBB breakdown was determined by Evans blue extravasation. There was a clear spatial relation between MMP-9 expressi...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Matrix metalloproteinase-9 and myeloperoxidase expression: quantitative analysis by antigen immunohistochemistry in a model of transient focal cerebral ischemia","attachmentId":40147655,"attachmentType":"pdf","work_url":"https://www.academia.edu/18594797/Matrix_metalloproteinase_9_and_myeloperoxidase_expression_quantitative_analysis_by_antigen_immunohistochemistry_in_a_model_of_transient_focal_cerebral_ischemia","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/18594797/Matrix_metalloproteinase_9_and_myeloperoxidase_expression_quantitative_analysis_by_antigen_immunohistochemistry_in_a_model_of_transient_focal_cerebral_ischemia"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="13451931" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/13451931/Increased_Brain_Expression_of_Matrix_Metalloproteinase_9_After_Ischemic_and_Hemorrhagic_Human_Stroke">Increased Brain Expression of Matrix Metalloproteinase-9 After Ischemic and Hemorrhagic Human Stroke</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32677912" href="https://independent.academia.edu/CarlosMolina55">Carlos Molina</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Stroke, 2006</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Increased Brain Expression of Matrix Metalloproteinase-9 After Ischemic and Hemorrhagic Human Stroke","attachmentId":45332127,"attachmentType":"pdf","work_url":"https://www.academia.edu/13451931/Increased_Brain_Expression_of_Matrix_Metalloproteinase_9_After_Ischemic_and_Hemorrhagic_Human_Stroke","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/13451931/Increased_Brain_Expression_of_Matrix_Metalloproteinase_9_After_Ischemic_and_Hemorrhagic_Human_Stroke"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="12993789" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/12993789/Early_upregulation_of_matrix_metalloproteinases_following_reperfusion_triggers_neuroinflammatory_mediators_in_brain_ischemia_in_rat">Early upregulation of matrix metalloproteinases following reperfusion triggers neuroinflammatory mediators in brain ischemia in rat</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32207660" href="https://uniromatre.academia.edu/GiorgioBernardi">Giorgio Bernardi</a></div><p class="ds-related-work--metadata ds2-5-body-xs">2007</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Early upregulation of matrix metalloproteinases following reperfusion triggers neuroinflammatory mediators in brain ischemia in rat","attachmentId":45793331,"attachmentType":"pdf","work_url":"https://www.academia.edu/12993789/Early_upregulation_of_matrix_metalloproteinases_following_reperfusion_triggers_neuroinflammatory_mediators_in_brain_ischemia_in_rat","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/12993789/Early_upregulation_of_matrix_metalloproteinases_following_reperfusion_triggers_neuroinflammatory_mediators_in_brain_ischemia_in_rat"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="33718248" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/33718248/Differential_alterations_in_the_expression_and_activity_of_matrix_metalloproteinases_2_and_9_after_transient_cerebral_ischemia_in_mice">Differential alterations in the expression and activity of matrix metalloproteinases 2 and 9 after transient cerebral ischemia in mice</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="66014727" href="https://independent.academia.edu/SarahGeorge40">Sarah George</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Neurobiology of Disease, 2004</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Differential alterations in the expression and activity of matrix metalloproteinases 2 and 9 after transient cerebral ischemia in mice","attachmentId":53714994,"attachmentType":"pdf","work_url":"https://www.academia.edu/33718248/Differential_alterations_in_the_expression_and_activity_of_matrix_metalloproteinases_2_and_9_after_transient_cerebral_ischemia_in_mice","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/33718248/Differential_alterations_in_the_expression_and_activity_of_matrix_metalloproteinases_2_and_9_after_transient_cerebral_ischemia_in_mice"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="26745078" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/26745078/Early_reperfusion_injury_is_associated_to_MMP2_and_IL_1%CE%B2_elevation_in_cortical_neurons_of_rats_subjected_to_middle_cerebral_artery_occlusion">Early reperfusion injury is associated to MMP2 and IL-1β elevation in cortical neurons of rats subjected to middle cerebral artery occlusion</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="46811561" href="https://bham.academia.edu/MichelangeloCerto">Dr Michelangelo Certo</a></div><p class="ds-related-work--abstract ds2-5-body-sm">—The pathophysiological processes implicated in ischemic brain damage are strongly affected by an inflam-matory reaction characterized by activation of immune cells and release of soluble mediators, including cytokines and chemokines. The pro-inflammatory cytokine interleukin (IL)-1b has been implicated in ischemic brain injury, however , to date, the mechanisms involved in the maturation of this cytokine in the ischemic brain have not been completely elucidated. We have previously suggested that matrix metalloproteinases (MMPs) may be implicated in cytokine production under pathological conditions. Here, we demonstrate that significant elevation of IL-1b occurs in the cortex as early as 1 h after the beginning of reperfu-sion in rats subjected to 2-h middle cerebral artery occlusion (MCAo). At this early stage, we observe increased expression of IL-1b in pericallosal astroglial cells and in cor-tical neurons and this latter signal colocalizes with elevated gelatinolytic activity. By gel zymography, we demonstrate that the increased gelatinolytic signal at 1-h reperfusion is mainly ascribed to MMP2. Thus, MMP2 seems to contribute to early brain elevation of IL-b after transient ischemia and this mechanism may promote damage since pharmacological inhibition of gelatinases by the selective MMP2/MMP9 inhibitor V provides neuroprotection in rats subjected to transient MCAo.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Early reperfusion injury is associated to MMP2 and IL-1β elevation in cortical neurons of rats subjected to middle cerebral artery occlusion","attachmentId":47024544,"attachmentType":"pdf","work_url":"https://www.academia.edu/26745078/Early_reperfusion_injury_is_associated_to_MMP2_and_IL_1%CE%B2_elevation_in_cortical_neurons_of_rats_subjected_to_middle_cerebral_artery_occlusion","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/26745078/Early_reperfusion_injury_is_associated_to_MMP2_and_IL_1%CE%B2_elevation_in_cortical_neurons_of_rats_subjected_to_middle_cerebral_artery_occlusion"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="116955806" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/116955806/Up_regulation_of_brain_cytokines_and_metalloproteinases_1_and_2_contributes_to_neurological_deficit_and_brain_damage_in_transient_ischemic_stroke">Up-regulation of brain cytokines and metalloproteinases 1 and 2 contributes to neurological deficit and brain damage in transient ischemic stroke</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="35700792" href="https://independent.academia.edu/EdnaConstanzaGomezVictoria">Edna Constanza Gomez Victoria</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Microvascular Research, 2020</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Up-regulation of brain cytokines and metalloproteinases 1 and 2 contributes to neurological deficit and brain damage in transient ischemic stroke","attachmentId":112942137,"attachmentType":"pdf","work_url":"https://www.academia.edu/116955806/Up_regulation_of_brain_cytokines_and_metalloproteinases_1_and_2_contributes_to_neurological_deficit_and_brain_damage_in_transient_ischemic_stroke","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/116955806/Up_regulation_of_brain_cytokines_and_metalloproteinases_1_and_2_contributes_to_neurological_deficit_and_brain_damage_in_transient_ischemic_stroke"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":40358259,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":40358259,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_40358259" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. 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ds2-5-body-sm ds2-5-body-link" data-author-id="46354116" href="https://independent.academia.edu/EmiriMandeville">Emiri Mandeville</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Cerebral Blood Flow &amp; Metabolism, 2006</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Astrocytic Induction of Matrix Metalloproteinase-9 and Edema in Brain Hemorrhage","attachmentId":97097391,"attachmentType":"pdf","work_url":"https://www.academia.edu/94717053/Astrocytic_Induction_of_Matrix_Metalloproteinase_9_and_Edema_in_Brain_Hemorrhage","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" 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data-author-id="32636054" href="https://independent.academia.edu/StevenGoldman1">Steven Goldman</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Acta Neurochirurgica, 2009</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Early activation of matrix metalloproteinase-9 is associated with blood–brain barrier disruption after photothrombotic cerebral ischemia in rats","attachmentId":86624092,"attachmentType":"pdf","work_url":"https://www.academia.edu/80144000/Early_activation_of_matrix_metalloproteinase_9_is_associated_with_blood_brain_barrier_disruption_after_photothrombotic_cerebral_ischemia_in_rats","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link 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class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="37629912" href="https://usc-es.academia.edu/JosePumar">Jose Pumar</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Stroke, 2003</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Plasma Metalloproteinase-9 Concentration Predicts Hemorrhagic Transformation in Acute Ischemic Stroke * Editorial Comment","attachmentId":39676236,"attachmentType":"pdf","work_url":"https://www.academia.edu/17726237/Plasma_Metalloproteinase_9_Concentration_Predicts_Hemorrhagic_Transformation_in_Acute_Ischemic_Stroke_Editorial_Comment","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link 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data-author-id="12533481" href="https://independent.academia.edu/Jos%C3%A9Castillo5">José Castillo</a></div><p class="ds-related-work--metadata ds2-5-body-xs">2010</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Plasma Metalloproteinase-9 Concentration Predicts Hemorrhagic Transformation in Acute Ischemic Stroke","attachmentId":33839732,"attachmentType":"pdf","work_url":"https://www.academia.edu/7216455/Plasma_Metalloproteinase_9_Concentration_Predicts_Hemorrhagic_Transformation_in_Acute_Ischemic_Stroke","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/7216455/Plasma_Metalloproteinase_9_Concentration_Predicts_Hemorrhagic_Transformation_in_Acute_Ischemic_Stroke"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="6" data-entity-id="64909153" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/64909153/Inhibition_of_Matrix_Metalloproteinase_9_Reduces_Infarct_Size_Matrix_Metalloproteinase_Expression_Increases_After_Cerebral_Focal_Ischemia_in_Rats">Inhibition of Matrix Metalloproteinase-9 Reduces Infarct Size Matrix Metalloproteinase Expression Increases After Cerebral Focal Ischemia in Rats</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm 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translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/104769122/Chronic_Cerebral_Hypoperfusion_Induces_MMP_2_but_Not_MMP_9_Expression_in_the_Microglia_and_Vascular_Endothelium_of_White_Matter"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="8" data-entity-id="13451927" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/13451927/Matrix_Metalloproteinase_Expression_After_Human_Cardioembolic_Stroke_Temporal_Profile_and_Relation_to_Neurological_Impairment">Matrix Metalloproteinase Expression After Human Cardioembolic Stroke: Temporal Profile and Relation to Neurological Impairment</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32677912" href="https://independent.academia.edu/CarlosMolina55">Carlos Molina</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Stroke, 2001</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Matrix Metalloproteinase Expression After Human Cardioembolic Stroke: Temporal Profile and Relation to Neurological Impairment","attachmentId":45332133,"attachmentType":"pdf","work_url":"https://www.academia.edu/13451927/Matrix_Metalloproteinase_Expression_After_Human_Cardioembolic_Stroke_Temporal_Profile_and_Relation_to_Neurological_Impairment","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" 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class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="78076031" href="https://mayoclinic.academia.edu/MBellolio">M. Fernanda Bellolio</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Stroke and Cerebrovascular Diseases, 2011</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Matrix Metalloproteinase-9 as a Marker for Acute Ischemic Stroke: A Systematic Review","attachmentId":71348988,"attachmentType":"pdf","work_url":"https://www.academia.edu/55513353/Matrix_Metalloproteinase_9_as_a_Marker_for_Acute_Ischemic_Stroke_A_Systematic_Review","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" 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href="https://independent.academia.edu/EmiriMandeville">Emiri Mandeville</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Stroke, 2005</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Tissue Plasminogen Activator Promotes Matrix Metalloproteinase-9 Upregulation After Focal Cerebral Ischemia","attachmentId":97097395,"attachmentType":"pdf","work_url":"https://www.academia.edu/94717063/Tissue_Plasminogen_Activator_Promotes_Matrix_Metalloproteinase_9_Upregulation_After_Focal_Cerebral_Ischemia","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/94717063/Tissue_Plasminogen_Activator_Promotes_Matrix_Metalloproteinase_9_Upregulation_After_Focal_Cerebral_Ischemia"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="12" data-entity-id="85288621" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/85288621/Early_matrix_metalloproteinase_9_concentration_in_the_first_48_h_after_aneurysmal_subarachnoid_haemorrhage_predicts_delayed_cerebral_ischaemia_An_observational_study">Early matrix metalloproteinase-9 concentration in the first 48 h after aneurysmal subarachnoid haemorrhage predicts delayed cerebral ischaemia: An observational study</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="41894720" href="https://independent.academia.edu/JeanCharlesMartin1">Jean-Charles Martin</a></div><p class="ds-related-work--metadata ds2-5-body-xs">European journal of anaesthesiology, 2016</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Early matrix metalloproteinase-9 concentration in the first 48 h after aneurysmal subarachnoid haemorrhage predicts delayed cerebral ischaemia: An observational study","attachmentId":90032105,"attachmentType":"pdf","work_url":"https://www.academia.edu/85288621/Early_matrix_metalloproteinase_9_concentration_in_the_first_48_h_after_aneurysmal_subarachnoid_haemorrhage_predicts_delayed_cerebral_ischaemia_An_observational_study","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" 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href="https://www.academia.edu/92850954/Melatonin_decreases_matrix_metalloproteinase_9_activation_and_expression_and_attenuates_reperfusion_induced_hemorrhage_following_transient_focal_cerebral_ischemia_in_rats">Melatonin decreases matrix metalloproteinase-9 activation and expression and attenuates reperfusion-induced hemorrhage following transient focal cerebral ischemia in rats</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="118582829" href="https://tzuchi.academia.edu/%E5%AE%97%E9%B7%B9%E9%99%B3">宗鷹陳</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Pineal Research, 2008</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Melatonin decreases matrix metalloproteinase-9 activation and expression and attenuates reperfusion-induced 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