Neutrophil Infiltration Increases Matrix Metalloproteinase-9 in the Ischemic Brain after Occlusion/Reperfusion of the Middle Cerebral Artery in Rats
Open Access
- 1 December 2003
- journal article
- Published by SAGE Publications in Journal of Cerebral Blood Flow & Metabolism
- Vol. 23 (12), 1430-1440
- https://doi.org/10.1097/01.wcb.0000090680.07515.c8
Abstract
Matrix metalloproteinase-9 (MMP-9) activity increases in the brain during the first day after focal ischemia and might be involved in the pathogenesis of tissue damage. 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. One-hour 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.Keywords
This publication has 34 references indexed in Scilit:
- S-Nitrosylation of Matrix Metalloproteinases: Signaling Pathway to Neuronal Cell DeathScience, 2002
- Examination of Several Potential Mechanisms for the Negative Outcome in a Clinical Stroke Trial of Enlimomab, a Murine Anti-Human Intercellular Adhesion Molecule-1 Antibody: A Bedside-to-Bench StudyStroke, 2001
- Effects of Matrix Metalloproteinase-9 Gene Knock-Out on the Proteolysis of Blood–Brain Barrier and White Matter Components after Cerebral IschemiaJournal of Neuroscience, 2001
- Role for Matrix Metalloproteinase 9 after Focal Cerebral Ischemia: Effects of Gene Knockout and Enzyme Inhibition with BB-94Journal of Cerebral Blood Flow & Metabolism, 2000
- Modulation by Nitric Oxide of Cerebral Neutrophil Accumulation after Transient Focal Ischemia in RatsJournal of Cerebral Blood Flow & Metabolism, 2000
- Early appearance of activated matrix metalloproteinase-9 and blood–brain barrier disruption in mice after focal cerebral ischemia and reperfusionBrain Research, 1999
- Early Appearance of Activated Matrix Metalloproteinase-9 after Focal Cerebral Ischemia in Mice: A Possible Role in Blood—Brain Barrier DysfunctionJournal of Cerebral Blood Flow & Metabolism, 1999
- Granules of the Human Neutrophilic Polymorphonuclear LeukocyteBlood, 1997
- Antibodies against Adhesion Molecules Reduce Apoptosis after Transient Middle Cerebral Artery Occlusion in Rat BrainJournal of Cerebral Blood Flow & Metabolism, 1996
- Measurement of Cutaneous Inflammation: Estimation of Neutrophil Content with an Enzyme MarkerJournal of Investigative Dermatology, 1982