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A Hydroxypyrone-Based Inhibitor of Metalloproteinase-12 Displays Neuroprotective Properties in Both Status Epilepticus and Optic Nerve Crush Animal Models

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dc.contributor.authorVinet, Jonathan
dc.contributor.authorCosta, Anna Maria
dc.contributor.authorLeo, Giuseppina
dc.contributor.authorMoons, Lieve
dc.contributor.authorArckens, Lutgarde
dc.contributor.authorBiagini, Giuseppe
dc.contributor.authorSalinas Navarro, Manuel Ángel
dc.contributor.departmentAnatomía Humana y Psicobiología
dc.date.accessioned2026-03-05T09:41:25Z
dc.date.available2026-03-05T09:41:25Z
dc.date.copyright© 2018 by the authors
dc.date.issued2018-07-25
dc.description.abstractRecently, we showed that matrix metalloproteinase-12 (MMP-12) is highly expressed in microglia and myeloid infiltrates, which are presumably involved in blood–brain barrier (BBB) leakage and subsequent neuronal cell death that follows status epilepticus (SE). Here, we assessed the effects of a hydroxypyrone-based inhibitor selective for MMP-12 in the pilocarpine-induced SE rat model to determine hippocampal cell survival. In the hippocampus of rats treated with pilocarpine, intra-hippocampal injections of the MMP-12 inhibitor protected Cornu Ammonis 3 (CA3) and hilus of dentate gyrus neurons against cell death and limited the development of the ischemic-like lesion that typically develops in the CA3 stratum lacunosum-moleculare of the hippocampus. Furthermore, we showed that MMP-12 inhibition limited immunoglobulin G and albumin extravasation after SE, suggesting a reduction in BBB leakage. Finally, to rule out any possible involvement of seizure modulation in the neuroprotective effects of MMP-12 inhibition, neuroprotection was also observed in the retina of treated animals after optic nerve crush. Overall, these results support the hypothesis that MMP-12 inhibition can directly counteract neuronal cell death and that the specific hydroxypyrone-based inhibitor used in this study could be a potential therapeutic agent against neurological diseases/disorders characterized by an important inflammatory response and/or neuronal cell loss.
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dc.format.extent16
dc.identifier.citationVinet, J., Costa, A. M., Salinas-Navarro, M., Leo, G., Moons, L., Arckens, L., & Biagini, G. (2018). A hydroxypyrone-based inhibitor of metalloproteinase-12 displays neuroprotective properties in both status epilepticus and optic nerve crush animal models. International Journal of Molecular Sciences, 19(8), 2178.
dc.identifier.doihttps://doi.org/10.3390/ijms19082178
dc.identifier.eissn1422-0067
dc.identifier.issn1661-6596
dc.identifier.urihttp://hdl.handle.net/10201/218362
dc.languageeng
dc.publisherMDPI
dc.relationThis research was funded by the Italian Ministry of Education, University and Research (MIUR, FFABR2017 to G.B.), by the KU Leuven Research Council (BOF-OT/10/033 to L.M.), the Hercules Foundation (AKUL-09-038; G0F0614N to L.M. and L.A.), and the Research Foundation Flanders (G.05311.10 to L.M.). J.V. is a postdoctoral fellow of the Umberto Veronesi Foundation (https://www.fondazioneveronesi.it/). M.S.N. is a postdoctoral research fellow of the Research Foundation Flanders.
dc.relation.publisherversionhttps://www.mdpi.com/1422-0067/19/8/2178
dc.rightsAttribution 4.0 International*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectStatus epilepticus
dc.subjectOptical neuropathy
dc.subjectBlood brain barrier leakage
dc.subjectMetalloproteinase 12
dc.subjectPilocarpine
dc.subjectRetinal ganglion cells
dc.subject.odsNo relacionado con ningún objetivo de desarrollo sostenible
dc.titleA Hydroxypyrone-Based Inhibitor of Metalloproteinase-12 Displays Neuroprotective Properties in Both Status Epilepticus and Optic Nerve Crush Animal Models
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublicationes
relation.isAuthorOfPublication81da925b-fa46-4a1a-96fd-ce35568fa423
relation.isAuthorOfPublication.latestForDiscovery81da925b-fa46-4a1a-96fd-ce35568fa423
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