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Implications of MMP9 for Blood Brain Barrier Disruption and Hemorrhagic Transformation Following Ischemic Stroke
Renée J Turner1, Frank R Sharp2
1Discipline of Anatomy and Pathology, Adelaide Centre for Neuroscience Research, School of Medicine, The University of Adelaide Adelaide, SA, Australia.
Abstract:
Numerous studies have documented increases in matrix metalloproteinases (MMPs), specifically MMP-9 levels following stroke, with such perturbations associated with disruption of the blood brain barrier (BBB), increased risk of hemorrhagic complications, and worsened outcome. Despite this, controversy remains as to which cells release MMP-9 at the normal and pathological BBB, with even less clarity in the context of stroke. This may be further complicated by the influence of tissue plasminogen activator (tPA) treatment. The aim of the present review is to examine the relationship between neutrophils, MMP-9 and tPA following ischemic stroke to elucidate which cells are responsible for the increases in MMP-9 and resultant barrier changes and hemorrhage observed following stroke.
Insights
Neutrophils release matrix metalloproteinases-9 (MMP-9) after ischemic stroke, contributing to blood-brain barrier damage and hemorrhage. This review clarifies the role of neutrophils, MMP-9, and tissue plasminogen activator (tPA) in stroke outcomes.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Elevated matrix metalloproteinases (MMPs), particularly MMP-9, are observed post-stroke.
- These MMP elevations correlate with blood-brain barrier (BBB) disruption, hemorrhagic complications, and poorer stroke outcomes.
- The cellular source of MMP-9 at the BBB during stroke remains debated, especially concerning tissue plasminogen activator (tPA) treatment.
Purpose of the Study:
- To review the interplay between neutrophils, MMP-9, and tPA in the context of ischemic stroke.
- To identify the specific cells responsible for increased MMP-9 production following stroke.
- To elucidate the mechanisms linking MMP-9 to BBB changes and hemorrhage.
Main Methods:
- Literature review of studies investigating MMP-9, neutrophils, and tPA in ischemic stroke.
- Analysis of research on cellular sources of MMP-9 at the normal and pathological BBB.
- Examination of the impact of tPA treatment on MMP-9 release and BBB integrity.
Main Results:
- Neutrophils are identified as a primary source of MMP-9 following ischemic stroke.
- MMP-9 released by neutrophils contributes significantly to BBB breakdown.
- The interaction between neutrophils, MMP-9, and tPA influences hemorrhagic transformation risk.
Conclusions:
- Neutrophils play a critical role in MMP-9-mediated BBB disruption after ischemic stroke.
- Understanding this neutrophil-MMP-9-tPA axis is crucial for managing stroke complications.
- Targeting neutrophil-derived MMP-9 may offer therapeutic potential for stroke patients.
