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Role of matrix metalloproteinases and therapeutic benefits of their inhibition in spinal cord injury.
Open accessAbstract
This review will focus on matrix metalloproteinases (MMPs) and their inhibitors in the context of spinal cord injury (SCI). MMPs have a specific cellular and temporal pattern of expression in the injured spinal cord. Here we consider their diverse functions in the acutely injured cord and during wound healing. Excessive activity of MMPs, and in particular gelatinase B (MMP-9), in the acutely injured cord contributes to disruption of the blood-spinal cord barrier, and the influx of leukocytes into the injured cord, as well as apoptosis. MMP-9 and MMP-2 regulate inflammation and neuropathic pain after peripheral nerve injury and may contribute to SCI-induced pain. Early pharmacologic inhibition of MMPs or the gelatinases (MMP-2 and MMP-9) results in an improvement in long-term neurological recovery and is associated with reduced glial scarring and neuropathic pain. During wound healing, gelatinase A (MMP-2) plays a critical role in limiting the formation of an inhibitory glial scar, and mice that are genetically deficient in this protease showed impaired recovery. Together, these findings illustrate complex, temporally distinct roles of MMPs in SCIs. As early gelatinase activity is detrimental, there is an emerging interest in developing gelatinase-targeted therapeutics that would be specifically tailored to the acute injured spinal cord. Thus, we focus this review on the development of selective gelatinase inhibitors.
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“MMP-9 may be responsible for this ECM reorganization”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Zhang et al., 2011
In the citing paper
“a number of studies have demonstrated increased MMP-9 levels following CNS injury and stroke in humans as well as animal models (Zhang et al., 2011; Chaturvedi and Kaczmarek, 2014; Liu et al., 2014).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Zhang et al., 2011
In the citing paper
“Quantitative PCR analysis indicates that transcripts from MMP-9, 3, 7, and 14 are upregulated in rodent models of spinal cord injury (Zhang et al., 2011).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Zhang et al., 2011
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Metadata
- Authors
- Zhang, H., Chang, M., Hansen, C. N., Basso, D. M., & Noble-Haeusslein, L. J.
- Affiliations
- University of California, San Francisco (US)
- University of Notre Dame (US)
- The Ohio State University (US)
- Corresponding author
- Zhang, Haoqian
- Venue
- Neurotherapeutics
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 8
- Issue
- 2
- Pages
- 206-220
- ISSN
- 1878-7479 (ISSN-L)
- PMC
- PMC3077748
- OpenAlex
- W2101966356
- Cited by
- 163
- References
- 105
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 10 · 2023: 9 · 2022: 14 · 2021: 15 · 2020: 6 · 2019: 11 · 2018: 6 · 2017: 7 · 2016: 9 · 2015: 10 · 2014: 19 · 2013: 13 · 2012: 13
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neurotherapeutics (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R01CA122417)
- National Institute of Neurological Disorders and Stroke (R21NS065937, R01NS050159, R01NS039278, RC1NS068200)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Spinal Cord Injury Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- matrix metalloproteinases, spinal cord injury, gelatinase inhibitors, MMP-9, MMP-2, blood-spinal cord barrier, leukocyte infiltration, apoptosis, neuropathic pain, glial scar, wound healing, neurological recovery
- MeSH terms
- Animals, Enzyme Inhibitors, Humans, Neuralgia, Spinal Cord Injuries, Matrix Metalloproteinases
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