title: Increased metalloproteinase activity in the hippocampus following status epilepticus.
abstract: 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.
authors.affiliation: Department of Neurology, School of Medicine, Stanford University, 1201 Welch Road, P211 MSLS, Stanford CA 94305, United States.
authors.forename: Deepti
authors.initials: D
authors.lastname: Dubey
authors.affiliation: The Children's Hospital of Philadelphia, Department of Pediatrics and Division of Neurology, 34th and Civic Center Boulevard, Philadelphia PA 19104, United States.
authors.forename: Paulette A
authors.initials: PA
authors.lastname: McRae
authors.affiliation: Department of Neurology, School of Medicine, Stanford University, 1201 Welch Road, P211 MSLS, Stanford CA 94305, United States.
authors.forename: Elyse K
authors.initials: EK
authors.lastname: Rankin-Gee
authors.affiliation: The Children's Hospital of Philadelphia, Department of Pediatrics and Division of Neurology, 34th and Civic Center Boulevard, Philadelphia PA 19104, United States.
authors.forename: Esther
authors.initials: E
authors.lastname: Baranov
authors.affiliation: The Children's Hospital of Philadelphia, Department of Pediatrics and Division of Neurology, 34th and Civic Center Boulevard, Philadelphia PA 19104, United States.
authors.forename: Luke
authors.initials: L
authors.lastname: Wandrey
authors.affiliation: The Children's Hospital of Philadelphia, Department of Pediatrics and Division of Neurology, 34th and Civic Center Boulevard, Philadelphia PA 19104, United States.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Rogers
authors.affiliation: Department of Neurology, School of Medicine, Stanford University, 1201 Welch Road, P211 MSLS, Stanford CA 94305, United States; The Children's Hospital of Philadelphia, Department of Pediatrics and Division of Neurology, 34th and Civic Center Boulevard, Philadelphia PA 19104, United States. Electronic address: brenda2@stanford.edu.
authors.forename: Brenda E
authors.initials: BE
authors.lastname: Porter
mesh_terms: D053674:Aggrecans / Q000378:metabolism; D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D007395:Interneurons / Q000378:metabolism; D008297:Male; D045726:Metalloproteases / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D010320:Parvalbumins / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000378:metabolism; D013226:Status Epilepticus / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D053674:Aggrecans; D010320:Parvalbumins; D045726:Metalloproteases
keywords: ADAMTS; Epilepsy; Matrix metalloproteinase; Perineuronal net; Status epilepticus