ArticleExperimental neurology2016
Deficiency in matrix metalloproteinase-2 results in long-term vascular instability and regression in the injured mouse spinal cord.
Article in Experimental neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Molecular Determinants of Bone Plasticity Regeneration After Trauma: Forensic Consequences.International journal of molecular sciences · 2025Review
- The neurovascular unit in healthy and injured spinal cord.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Review
- Early mobilization in spinal cord injury promotes changes in microglial dynamics and recovery of motor function.IBRO neuroscience reports · 2022Article
- Lymphatic Vessel Regression and Its Therapeutic Applications: Learning From Principles of Blood Vessel Regression.Frontiers in physiology · 2022Review
- Tumor necrosis factor α, protein gene product 9.5, matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 presence in congenital intra-abdominal adhesions in children under one year of age.Archives of medical science : AMS · 2021Article
- Different roles of matrix metalloproteinase 2 in osteolysis of skeletal dysplasia and bone metastasis (Review).Molecular medicine reports · 2021Review
- Neuroinflammatory responses of microglia in central nervous system trauma.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Review
- Protein Degradome of Spinal Cord Injury: Biomarkers and Potential Therapeutic Targets.Molecular neurobiology · 2020Review
- Neuroectodermal Stem Cells Grafted into the Injured Spinal Cord Induce Both Axonal Regeneration and Morphological Restoration via Multiple Mechanisms.Journal of neurotrauma · 2019Article
- Matrix metalloproteinase signals following neurotrauma are right on cue.Cellular and molecular life sciences : CMLS · 2019Review
- Overexpression of MMPs in Corneas Requiring Penetrating and Deep Anterior Lamellar Keratoplasty.Investigative ophthalmology & visual science · 2019Article
- Glial Cells Shape Pathology and Repair After Spinal Cord Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2018Review
- The Role of Biomaterials as Angiogenic Modulators of Spinal Cord Injury: Mimetics of the Spinal Cord, Cell and Angiogenic Factor Delivery Agents.Frontiers in pharmacology · 2018Review
- Role of matrix metalloproteinases in bone regeneration: Narrative review.Journal of oral biology and craniofacial researchReview
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Angiogenesis plays a critical role in wound healing after spinal cord injury. Therefore, understanding the events that regulate angiogenesis has considerable relevance from a therapeutic standpoint. We evaluated the contribution of matrix metalloproteinase (MMP)-2 to angiogenesis and vascular stability in spinal cord injured MMP-2 knockout and wildtype (WT) littermates. While MMP-2 deficiency resulted in reduced endothelial cell division within the lesioned epicenter, there were no genotypic differences in vascularity (vascular density, vascular area, and endothelial cell number) over the first two weeks post-injury. However, by 21days post-injury MMP-2 deficiency resulted in a sharp decline in vascularity, indicative of vascular regression. Complementary in vitro studies of brain capillary endothelial cells confirmed MMP-2 dependent proliferation and tube formation. As deficiency in MMP-2 led to prolonged MMP-9 expression in the injured spinal cord, we examined both short-term and long-term exposure to MMP-9 in vitro. While MMP-9 supported endothelial tube formation and proliferation, prolonged exposure resulted in loss of tubes, findings consistent with vascular regression. Vascular instability is frequently associated with pericyte dissociation and precedes vascular regression. Quantification of PDGFrβ+ pericyte coverage of mature vessels within the glial scar (the reactive gliosis zone), a known source of MMP-9, revealed reduced coverage in MMP-2 deficient animals. These findings suggest that acting in the absence of MMP-2, MMP-9 transiently supports angiogenesis during the early phase of wound healing while its prolonged expression leads to vascular instability and regression. These findings should be considered while developing therapeutic interventions that block MMPs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.