Increased metalloproteinase activity in the hippocampus following status epilepticus
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Increased neuronal plasticity and neuronal cell loss has been implicated in the development of epilepsy following injury. Parvalbumin fast spiking inhibitory interneurons have a robust extracellular matrix coating their cell bodies and the proximal dendrites called the perineuronal net (PNN). The role of the PNN is not clear but it has been implicated in closing of the critical period, altering seizure thresholds and providing neuronal protection from oxidative stress. The PNN is susceptible to degradation following a prolonged seizure and there is an increase in proteolytic-fragments of the PNN enriched proteoglycan aggrecan (Dzwonek et al., 2004). Here we demonstrate an increase in matrix metalloproteinase (MMP) activity in the hippocampus following status epilepticus (SE). We further assessed MMP3 and 13, two of 24 identified MMPs, both MMP3 and 13 mRNA increase in the hippocampus after SE and MMP13 activity increases by functional assay as well as it co-localizes with PNN in rat brain. In contrast, two of the brain expressed ADAMTS (A Disintegrin And Metalloproteinase with ThromboSpondin motifs) also implicated in aggrecan degradation, did not consistently increase following SE though ADAMTS4 is highly expressed in glia and ADAMTS5 in neuronal cell bodies and their processes. The increase in MMP activity following SE suggests that in the future studies, MMP inhibitors are candidates for blocking PNN degradation and assessing the role of the PNN loss in epileptogenesis and cellular function.
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Heightened MMP activity has been reported in other models of epilepsy, with elevated MMP level associated with epileptiform activity.
“While we suggest a pivotal role for the MMP activity in glioma-associated epilepsy, heightened MMP activity has also been reported in other models of epilepsy46 with elevated MMP level being associated with epileptiform activity47–50.”
From Perineuronal nets decrease membrane capacitance of peritumoral fast spiking interneurons in a model of epilepsy (2018) · cites this paper as [46]
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- Authors
- Dubey, D., McRae, P. A., Rankin-Gee, E. K., Baranov, E., Wandrey, L., Rogers, S., & Porter, B. E.
- Affiliations
- Stanford Medicine (US)
- Children's Hospital of Philadelphia (US)
- Corresponding author
- Porter, Brenda E.
- Venue
- Epilepsy Research
- Publisher
- Elsevier BV
- Published
- 2017-05
- Volume
- 132
- Pages
- 50-58
- ISSN
- 0920-1211 (ISSN-L)
- PMC
- PMC6690398
- OpenAlex
- W2591727464
- Cited by
- 65
- References
- 44
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 8 · 2023: 6 · 2022: 9 · 2021: 6 · 2020: 6 · 2019: 6 · 2018: 9 · 2017: 4
- FWCI
- 5.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Epilepsy Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS056222)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- status epilepticus, matrix metalloproteinases, perineuronal nets, hippocampus, MMP-3, MMP-13, ADAMTS, aggrecan degradation, extracellular matrix, epileptogenesis, parvalbumin interneurons, matrix metalloproteinase inhibitors
- MeSH terms
- Animals, Extracellular Matrix, Hippocampus, Interneurons, Male, Neuronal Plasticity, Parvalbumins, Seizures, Status Epilepticus, Rats, Sprague-Dawley, Metalloproteases, Aggrecans
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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