{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T02:25:42Z","timestamp":1788229542094,"version":"build-2803163510"},"reference-count":60,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2018,7,25]],"date-time":"2018-07-25T00:00:00Z","timestamp":1532476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["FFABR2017"],"award-info":[{"award-number":["FFABR2017"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004497","name":"Onderzoeksraad, KU Leuven","doi-asserted-by":"publisher","award":["BOF-OT\/10\/033"],"award-info":[{"award-number":["BOF-OT\/10\/033"]}],"id":[{"id":"10.13039\/501100004497","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012220","name":"Hercules Foundation","doi-asserted-by":"publisher","award":["AKUL-09-038"],"award-info":[{"award-number":["AKUL-09-038"]}],"id":[{"id":"10.13039\/100012220","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012220","name":"Hercules Foundation","doi-asserted-by":"publisher","award":["G0F0614N"],"award-info":[{"award-number":["G0F0614N"]}],"id":[{"id":"10.13039\/100012220","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G.05311.10"],"award-info":[{"award-number":["G.05311.10"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["post-doctoral fellowship to Manuel Salinas-Navarro"],"award-info":[{"award-number":["post-doctoral fellowship to Manuel Salinas-Navarro"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004710","name":"Fondazione Umberto Veronesi","doi-asserted-by":"publisher","award":["post-doctoral fellowship to Jonathan Vinet"],"award-info":[{"award-number":["post-doctoral fellowship to Jonathan Vinet"]}],"id":[{"id":"10.13039\/501100004710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Recently, we showed that matrix metalloproteinase-12 (MMP-12) is highly expressed in microglia and myeloid infiltrates, which are presumably involved in blood\u2013brain 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.<\/jats:p>","DOI":"10.3390\/ijms19082178","type":"journal-article","created":{"date-parts":[[2018,7,25]],"date-time":"2018-07-25T11:09:30Z","timestamp":1532516970000},"page":"2178","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["A Hydroxypyrone-Based Inhibitor of Metalloproteinase-12 Displays Neuroprotective Properties in Both Status Epilepticus and Optic Nerve Crush Animal Models"],"prefix":"10.3390","volume":"19","author":[{"given":"Jonathan","family":"Vinet","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Epileptology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3152-9890","authenticated-orcid":false,"given":"Anna-Maria","family":"Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Epileptology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Salinas-Navarro","sequence":"additional","affiliation":[{"name":"Laboratory of Neural Circuit Development and Regeneration, Department of Biology, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Leo","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Epileptology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lieve","family":"Moons","sequence":"additional","affiliation":[{"name":"Laboratory of Neural Circuit Development and Regeneration, Department of Biology, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutgarde","family":"Arckens","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroplasticity and Neuroproteomics, Department of Biology, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7130-2511","authenticated-orcid":false,"given":"Giuseppe","family":"Biagini","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Epileptology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"},{"name":"Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1016\/j.bbamcr.2017.05.010","article-title":"Matrix metalloproteinases as regulators of inflammatory processes","volume":"1864","author":"Fingleton","year":"2017","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"12189","DOI":"10.1074\/jbc.272.18.12189","article-title":"Hydrolysis of a broad spectrum of extracellular matrix proteins by human macrophage elastase","volume":"272","author":"Gronski","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1007\/s12035-017-0418-5","article-title":"MMP-12, a promising therapeutic target for neurological diseases","volume":"55","author":"Chelluboina","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10107","DOI":"10.1523\/JNEUROSCI.23-31-10107.2003","article-title":"An adverse role for matrix metallloproteinase 12 after spinal cord injury in mice","volume":"23","author":"Wells","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/S0165-5728(03)00036-5","article-title":"Matrix metalloproteinase-12 is expressed in phagocytotic macrophages in active multiple sclerosis lesions","volume":"138","author":"Vos","year":"2003","journal-title":"J. Neuroimmunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3523","DOI":"10.1161\/STROKEAHA.115.011031","article-title":"Matrix metalloproteinase-12 induces blood\u2013brain barrier damage after focal cerebral ischemia","volume":"46","author":"Chelluboina","year":"2015","journal-title":"Stroke"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9504","DOI":"10.1038\/srep09504","article-title":"Post-transcriptional inactivation of matrix metalloproteinase-12 after focal cerebral ischemia attenuates brain damage","volume":"5","author":"Chelluboina","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S1474-4422(02)00073-X","article-title":"Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy","volume":"1","author":"Sutula","year":"2002","journal-title":"Lancet Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/nrneurol.2010.178","article-title":"The role of inflammation in epilepsy","volume":"7","author":"Vezzani","year":"2011","journal-title":"Nat. Rev. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"663","DOI":"10.2174\/0929867320666131119152201","article-title":"Pathophysiology of mesial temporal lobe epilepsy: Is prevention of damage antiepileptogenic?","volume":"21","author":"Curia","year":"2014","journal-title":"Curr. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7369020","DOI":"10.1155\/2016\/7369020","article-title":"Matrix metalloproteinase 9 in epilepsy: The role of neuroinflammation in seizure development","volume":"2016","author":"Bronisz","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.nbd.2012.06.023","article-title":"Matrix metalloproteinase 9 regulates cell death following pilocarpine-induced seizures in the developing brain","volume":"48","author":"Hoehna","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3389\/fnana.2014.00068","article-title":"Matrix metalloproteinase-9 involvement in the structural plasticity of dendritic spines","volume":"8","author":"Stawarski","year":"2014","journal-title":"Front. Neuroanat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1002\/glia.23008","article-title":"Microglia are less pro-inflammatory than myeloid infiltrates in the hippocampus of mice exposed to status epilepticus","volume":"64","author":"Vinet","year":"2016","journal-title":"Glia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"510679","DOI":"10.1155\/2015\/510679","article-title":"Synthesis and validation of a hydroxypyrone-based, potent, and specific matrix metalloproteinase-12 inhibitor with anti-inflammatory activity in vitro and in vivo","volume":"2015","author":"Aerts","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Lucchi, C., Curia, G., Vinet, J., Gualtieri, F., Bresciani, E., Locatelli, V., Torsello, A., and Biagini, G. (2013). Protective but not anticonvulsant effects of ghrelin and JMV-1843 in the pilocarpine model of status epilepticus. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072716"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1097\/NEN.0b013e318181b8ae","article-title":"Proepileptic influence of a focal vascular lesion affecting entorhinal cortex-CA3 connections after status epilepticus","volume":"67","author":"Biagini","year":"2008","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.neuroscience.2012.05.018","article-title":"Increased perivascular laminin predicts damage to astrocytes in CA3 and piriform cortex following chemoconvulsive treatments","volume":"218","author":"Gualtieri","year":"2012","journal-title":"Neuroscience"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.eplepsyres.2009.03.005","article-title":"Blood-brain barrier breakdown-inducing astrocytic transformation: Novel targets for the prevention of epilepsy","volume":"85","author":"Friedman","year":"2009","journal-title":"Epilepsy Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1002\/glia.22311","article-title":"Blood-brain barrier dysfunction, TGF\u03b2 signaling, and astrocyte dysfunction in epilepsy","volume":"60","author":"Heinemann","year":"2012","journal-title":"Glia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/j.1528-1167.2012.03701.x","article-title":"Blood-brain barrier dysfunction-induced inflammatory signaling in brain pathology and epileptogenesis","volume":"53","author":"Kim","year":"2012","journal-title":"Epilepsia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1111\/jne.12063","article-title":"Neurosteroids and epileptogenesis","volume":"25","author":"Biagini","year":"2013","journal-title":"J. Neuroendocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.jneumeth.2008.04.019","article-title":"The pilocarpine model of temporal lobe epilepsy","volume":"172","author":"Curia","year":"2008","journal-title":"J. Neurosci. Methods"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.exer.2016.01.006","article-title":"Differential visual system organization and susceptibility to experimental models of optic neuropathies in three commonly used mouse strains","volume":"145","author":"Dekeyster","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Dekeyster, E., Geeraerts, E., Buyens, T., Van den Haute, C., Baekelandt, V., De Groef, L., Salinas-Navarro, M., and Moons, L. (2015). Tackling Glaucoma from within the Brain: An Unfortunate Interplay of BDNF and TrkB. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0142067"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.exer.2011.02.008","article-title":"Axotomy-induced retinal ganglion cell death in adult mice: Quantitative and topographic time course analyses","volume":"92","year":"2011","journal-title":"Exp. Eye Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.visres.2009.01.010","article-title":"Retinal ganglion cell population in adult albino and pigmented mice: A computerized analysis of the entire population and its spatial distribution","volume":"49","author":"Mayor","year":"2009","journal-title":"Vis. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.pneurobio.2016.08.002","article-title":"The multifaceted role of metalloproteinases in physiological and pathological conditions in embryonic and adult brains","volume":"155","author":"Herrero","year":"2017","journal-title":"Prog. Neurobiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6766","DOI":"10.2174\/1381612811319380009","article-title":"Inflammatory mediators in epilepsy","volume":"19","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4301","DOI":"10.1523\/JNEUROSCI.2751-17.2018","article-title":"Matrix Metalloproteinase-Mediated Blood-Brain Barrier Dysfunction in Epilepsy","volume":"38","author":"Rempe","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1016\/j.celrep.2014.10.064","article-title":"Pharmacogenetic inhibition of eIF4E-dependent Mmp9 mRNA translation reverses fragile X syndrome-like phenotypes","volume":"9","author":"Gkogkas","year":"2014","journal-title":"Cell Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/epi.13245","article-title":"Blood-brain barrier leakage after status epilepticus in rapamycin-treated rats II: Potential mechanisms","volume":"57","author":"Otte","year":"2016","journal-title":"Epilepsia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1038\/nm.1878","article-title":"A role for leukocyte-endothelial adhesion mechanisms in epilepsy","volume":"14","author":"Fabene","year":"2008","journal-title":"Nat. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.nbd.2007.08.012","article-title":"Innate and adaptive immunity during epileptogenesis and spontaneous seizures: Evidence from experimental models and human temporal lobe epilepsy","volume":"29","author":"Ravizza","year":"2008","journal-title":"Neurobiol. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"17151","DOI":"10.1073\/pnas.0806682105","article-title":"Microglial activation and TNFalpha production mediate altered CNS excitability following peripheral inflammation","volume":"105","author":"Riazi","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4037","DOI":"10.1523\/JNEUROSCI.6210-10.2011","article-title":"Brain infiltration of leukocytes contributes to the pathophysiology of temporal lobe epilepsy","volume":"31","author":"Zattoni","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1159\/000243083","article-title":"Kainic acid-activated microglia mediate increased excitability of rat hippocampal neurons in vitro and in vivo: Crucial role of interleukin-1beta","volume":"17","author":"Zheng","year":"2010","journal-title":"Neuroimmunomodulation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.neuroscience.2015.07.065","article-title":"ETB receptor-mediated MMP-9 activation induces vasogenic edema via ZO-1 protein degradation following status epilepticus","volume":"304","author":"Kim","year":"2015","journal-title":"Neuroscience"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0002-9440(10)65551-4","article-title":"Expression and localization of matrix metalloproteinase-12 in the aorta of cholesterol-fed rabbits: Relationship to lesion development","volume":"153","author":"Matsumoto","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.exger.2006.11.012","article-title":"Induction of matrix metalloproteinases (MMP3, MMP12 and MMP13) expression in the microglia by amyloid-beta stimulation via the PI3K\/Akt pathway","volume":"42","author":"Ito","year":"2007","journal-title":"Exp. Gerontol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.4103\/1673-5374.187059","article-title":"Differential temporal expression of matrix metalloproteinases following sciatic nerve crush","volume":"11","author":"Qin","year":"2016","journal-title":"Neural Regen. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1159\/000232561","article-title":"Expression of MMP-12 after neonatal hypoxic-ischemic brain injury in mice","volume":"31","author":"Svedin","year":"2009","journal-title":"Dev. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.neuroscience.2014.07.030","article-title":"Role of blood\u2013brain barrier in temporal lobe epilepsy and pharmacoresistance","volume":"277","author":"Aronica","year":"2014","journal-title":"Neuroscience"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1097\/01.jnen.0000229990.32795.0d","article-title":"MMP-12, MMP-3, and TIMP-1 are markedly upregulated in chronic demyelinating theiler murine encephalomyelitis","volume":"65","author":"Ulrich","year":"2006","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Qu, J., and Jakobs, T.C. (2013). The Time Course of Gene Expression during Reactive Gliosis in the Optic Nerve. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067094"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1167\/iovs.13-13374","article-title":"Retinal MMP-12, MMP-13, TIMP-1, and TIMP-2 expression in murine experimental retinal detachment","volume":"55","author":"Kim","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Li, J., Wang, J.J., Peng, Q., Chen, C., Humphrey, M.B., Heinecke, J., and Zhang, S.X. (2012). Macrophage metalloelastase (MMP-12) deficiency mitigates retinal inflammation and pathological angiogenesis in ischemic retinopathy. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0052699"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.expneurol.2015.04.004","article-title":"Enhanced expression of matrix metalloproteinase-12 contributes to Npc1 deficiency-induced axonal degeneration","volume":"269","author":"Liao","year":"2015","journal-title":"Exp. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/s12975-015-0425-7","article-title":"A Cannabinoid Receptor 2 Agonist Prevents Thrombin-Induced Blood-Brain Barrier Damage via the Inhibition of Microglial Activation and Matrix Metalloproteinase Expression in Rats","volume":"6","author":"Li","year":"2015","journal-title":"Transl. Stroke Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1002\/glia.23137","article-title":"HuR promotes the molecular signature and phenotype of activated microglia: Implications for amyotrophic lateral sclerosis and other neurodegenerative diseases","volume":"65","author":"Matsye","year":"2017","journal-title":"Glia"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"676","DOI":"10.3389\/fphar.2017.00676","article-title":"Involvement of PPAR\u03b3 in the anticonvulsant activity of EP-80317, a ghrelin receptor antagonist","volume":"8","author":"Lucchi","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/0013-4694(72)90177-0","article-title":"Modification of seizure activity by electrical stimulation. II. Motor seizure","volume":"32","author":"Racine","year":"1972","journal-title":"Electroencephalogr. Clin. Neurophysiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1111\/j.1528-1157.1999.tb00872.x","article-title":"Status epilepticus: An overview of the clinical problem","volume":"40","author":"Lowenstein","year":"1999","journal-title":"Epilepsia"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Giordano, C., Vinet, J., Curia, G., and Biagini, G. (2015). Repeated 6-Hz corneal stimulation progressively increases FosB\/\u0394FosB levels in the lateral amygdala and induces seizure generalization to the hippocampus. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0141221"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"281","DOI":"10.3389\/fncel.2016.00281","article-title":"Progressive seizure aggravation in the repeated 6-Hz corneal stimulation model is accompanied by marked increase in hippocampal p-ERK1\/2 immunoreactivity in neurons","volume":"10","author":"Giordano","year":"2016","journal-title":"Front. Cell. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s12017-012-8203-0","article-title":"Hypoxia markers are expressed in interneurons exposed to recurrent seizures","volume":"15","author":"Gualtieri","year":"2013","journal-title":"Neuromol. Med."},{"key":"ref_57","first-page":"2147","article-title":"A practical approach to optic nerve crush in the mouse","volume":"18","author":"Templeton","year":"2012","journal-title":"Mol. Vis."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Mead, B., Thompson, A., Scheven, B.A., Logan, A., Berry, M., and Leadbeater, W. (2014). Comparative evaluation of methods for estimating retinal ganglion cell loss in retinal sections and wholemounts. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110612"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3860","DOI":"10.1167\/iovs.08-3267","article-title":"Brn3a as a marker of retinal ganglion cells: Qualitative and quantitative time course studies in na\u00efve and optic nerve-injured retinas","volume":"50","author":"Agudo","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.exer.2016.04.010","article-title":"A freely available semi-automated method for quantifying retinal ganglion cells in entire retinal flatmounts","volume":"147","author":"Geeraerts","year":"2016","journal-title":"Exp. 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