Multiphasic roles for matrix metalloproteinases after stroke
Abstract
Matrix metalloproteinases (MMPs) comprise a family of zinc endopeptidases that play major roles in the physiology and pathology of the mammalian central nervous system (CNS). These proteinases are evolutionarily conserved as modulators of extracellular matrix during CNS development. After acute tissue injury such as that which occurs after stroke, MMPs become dysregulated and subsequently mediate acute neurovascular disruption and parenchymal destruction. Data from gene knockout models and pharmacologic experiments suggest that MMPs may be attractive therapeutic targets for stroke. However, emerging data now also suggest that some aspects of MMP activity during the delayed neuroinflammatory response may contribute to remodelling and stroke recovery. Ultimately, a more nuanced approach to modifying the MMP response after stroke may be needed in order to optimize inhibition during acute stages of injury without interfering with beneficial endogenous mechanisms of neurovascular remodelling.
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Similar findings about the importance of timing for administration of a neurorestorative therapy for stroke have been reported for VEGF and modulators of matrix metalloproteinases.
“Similar findings about the importance of timing for administration of a neurorestorative therapy for stroke have been reported for VEGF94 and modulators of matrix metallo proteinases.95”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [95]
The same enzymes later contribute to beneficial mechanisms of neurovascular remodeling.
“However, the same enzymes later contribute to beneficial mechanisms of neurovascular remodeling (Lo, 2008; Rosell and Lo, 2008; del Zoppo, 2010)”
From Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep (2017) · cites this paper as Rosell and Lo, 2008
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- Authors
- ROSELL, A., & LO, E.
- Affiliations
- Harvard University (US)
- Corresponding author
- ROSELL, A
- LO, E
- Venue
- Current Opinion in Pharmacology
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 8
- Issue
- 1
- Pages
- 82-89
- ISSN
- 1471-4892 (ISSN-L)
- OpenAlex
- W2010817955
- Cited by
- 215
- References
- 62
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 5 · 2022: 7 · 2021: 11 · 2020: 11 · 2019: 11 · 2018: 9 · 2017: 12 · 2016: 20 · 2015: 15 · 2014: 13 · 2013: 21 · 2012: 21
- FWCI
- 5.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- matrix metalloproteinases, stroke, extracellular matrix, neuroinflammation, matrix metalloproteinase inhibition, stroke recovery, therapeutic target
- MeSH terms
- Animals, Brain Ischemia, Humans, Neuronal Plasticity, Protease Inhibitors, Biomarkers, Stroke, Matrix Metalloproteinases, Matrix Metalloproteinase Inhibitors
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