{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:16:22Z","timestamp":1771028182640,"version":"3.50.1"},"reference-count":57,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2017,8,25]],"date-time":"2017-08-25T00:00:00Z","timestamp":1503619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP)","award":["2005\/60254-0"],"award-info":[{"award-number":["2005\/60254-0"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)"},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>(1) Background: Temporal lobe epilepsy (TLE) is the most common type of epilepsy in adults. It is also the one with the highest percentage of drug-resistance to the current available anti-epileptic drugs (AED). Additionaly, most antiepileptic drugs are only able to control seizures in epileptogenesis, but do not decrease the hippocampal neurodegenerative process. TLE patients have a reduced population of interneuronal cells, which express Parvalbumin (PV) proteins. This reduction is directly linked to seizure frequency and severity in the chronic period of epilepsy. There is therefore a need to seek new therapies with a disease-modifying profile, and with efficient antiepileptic and neuroprotective properties. Parawixin2, a compound isolated from the venom of the spider Parawixia bistriata, has been shown to inhibit GABA transporters (GAT) and to have acute anticonvulsant effects in rats. (2) Methods: In this work, we studied the effects of Parawixin2 and Tiagabine (an FDA- approved GAT inhibitor), and compared these effects in a TLE model. Rats were subjected to lithium-pilocarpine TLE model and the main features were evaluated over a chronic period including: (a) spontaneous recurrent seizures (SRS), (b) neuronal loss, and (c) PV cell density in different regions of the hippocampus (CA1, CA3, DG and Hilus). (3) Results: Parawixin2 treatment reduced SRS frequency whereas Tiagabine did not. We also found a significant reduction in neuronal loss in CA3 and in the hilus regions of the hippocampus, in animals treated with Parawixin2. Noteworthy, Parawixin2 significantly reversed PV cell loss observed particularly in DG layers. (4) Conclusions: Parawixin2 exerts a promising neuroprotective and anti-epileptic effect and has potential as a novel agent in drug design.<\/jats:p>","DOI":"10.3390\/toxins9090262","type":"journal-article","created":{"date-parts":[[2017,8,25]],"date-time":"2017-08-25T11:03:17Z","timestamp":1503658997000},"page":"262","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Disease Modifying Effects of the Spider Toxin Parawixin2 in the Experimental Epilepsy Model"],"prefix":"10.3390","volume":"9","author":[{"given":"L\u00edvea","family":"Godoy","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Neurobiologia e Pe\u00e7onhas (LNP), Faculdade de Filosofia, Ci\u00eancias e Letras de Ribeir\u00e3o Preto, Universidade de S\u00e3o Paulo, Av. Bandeirantes, 3900, CEP 14040-901 Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"},{"name":"Instituto de Neuroci\u00eancias e Comportamento (INEC), Av. do Caf\u00e9, 2450, CEP 14050-220 Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6538-8312","authenticated-orcid":false,"given":"Jos\u00e9","family":"Liberato","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Neurobiologia e Pe\u00e7onhas (LNP), Faculdade de Filosofia, Ci\u00eancias e Letras de Ribeir\u00e3o Preto, Universidade de S\u00e3o Paulo, Av. Bandeirantes, 3900, CEP 14040-901 Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"},{"name":"Instituto de Neuroci\u00eancias e Comportamento (INEC), Av. do Caf\u00e9, 2450, CEP 14050-220 Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5787-8533","authenticated-orcid":false,"given":"Marcus","family":"Celani","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Neurobiologia e Pe\u00e7onhas (LNP), Faculdade de Filosofia, Ci\u00eancias e Letras de Ribeir\u00e3o Preto, Universidade de S\u00e3o Paulo, Av. Bandeirantes, 3900, CEP 14040-901 Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo","family":"Gobbo-Neto","sequence":"additional","affiliation":[{"name":"N\u00facleo de Pesquisas em Produtos Naturais e Sint\u00e9ticos (NPPNS), Faculdade de Ci\u00eancias Farmac\u00eauticas de Ribeir\u00e3o Preto, Universidade de S\u00e3o Paulo, Av. do Cafe s\/n, CEP 14040-903 Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8159-3658","authenticated-orcid":false,"given":"Norberto","family":"Lopes","sequence":"additional","affiliation":[{"name":"N\u00facleo de Pesquisas em Produtos Naturais e Sint\u00e9ticos (NPPNS), Faculdade de Ci\u00eancias Farmac\u00eauticas de Ribeir\u00e3o Preto, Universidade de S\u00e3o Paulo, Av. do Cafe s\/n, CEP 14040-903 Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wagner","family":"Dos Santos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Neurobiologia e Pe\u00e7onhas (LNP), Faculdade de Filosofia, Ci\u00eancias e Letras de Ribeir\u00e3o Preto, Universidade de S\u00e3o Paulo, Av. Bandeirantes, 3900, CEP 14040-901 Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"},{"name":"Instituto de Neuroci\u00eancias e Comportamento (INEC), Av. do Caf\u00e9, 2450, CEP 14050-220 Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0014-2999(97)01514-8","article-title":"New visions in the pharmacology of anticonvulsion","volume":"342","year":"1998","journal-title":"Eur. J. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3389\/fncel.2013.00108","article-title":"Changes in the sensitivity of GABAA current rundown to drug treatments in a model of temporal lobe epilepsy","volume":"7","author":"Cifelli","year":"2013","journal-title":"Front. Cell. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.wneu.2016.12.074","article-title":"Prevalence and Incidence of Drug-Resistant Mesial Temporal Lobe Epilepsy in the United States","volume":"99","author":"Stewart","year":"2017","journal-title":"World Neurosurg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6650","DOI":"10.1523\/JNEUROSCI.22-15-06650.2002","article-title":"Axon sprouting in a model of temporal lobe epilepsy creates a predominantly excitatory feedback circuit","volume":"22","author":"Buckmaster","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1615\/CritRevNeurobiol.v18.i1-2.140","article-title":"Seizures beget seizures: The quest for GABA as a key player","volume":"18","year":"2006","journal-title":"Crit. Rev. Neurobiol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Anderson, S.A., and Baraban, S.C. (2012). Cell Therapy Using GABAergic Neural Progenitors. Jasper\u2032s Basic Mechanisms of the Epilepsies, Oxford University Press. [4th ed.].","DOI":"10.1093\/med\/9780199746545.003.0087"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/hipo.450010106","article-title":"Permanently altered hippocampal structure, excitability, and inhibition after experimental status epilepticus in the rat: The \u201cdormant basket cell\u201d hypothesis and its possible relevance to temporal lobe epilepsy","volume":"1","author":"Sloviter","year":"1991","journal-title":"Hippocampus"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.brainresbull.2006.08.009","article-title":"Drug resistance and hippocampal damage after delayed treatment of pilocarpine-induced epilepsy in the rat","volume":"71","author":"Chakir","year":"2006","journal-title":"Brain Res. Bull."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1093\/brain\/122.10.1807","article-title":"Chandelier cells and epilepsy","volume":"122","author":"DeFelipe","year":"1999","journal-title":"Brain"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Noebels, J.L., Avoli, M., Rogawski, M.A., Olsen, R.W., and Delgado-Escueta, A.V. (2012). Alterations in synaptic function in epilepsy. Jasper\u2019s Basic Mechanisms of the Epilepsies, Oxford University Press. [4th ed.].","DOI":"10.1093\/med\/9780199746545.001.0001"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.tins.2004.11.011","article-title":"Multiple facets of GABAergic neurons and synapses: Multiple fates of GABA signalling in epilepsies","volume":"28","author":"Cossart","year":"2005","journal-title":"Trends Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1097\/00019052-200104000-00009","article-title":"The process of epileptogenesis: A pathophysiological approach","volume":"14","author":"Dalby","year":"2001","journal-title":"Curr. Opin. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3S","DOI":"10.1111\/j.1365-2125.1989.tb03454.x","article-title":"GABAergic mechanisms in the pathogenesis and treatment of epilepsy","volume":"27","author":"Meldrum","year":"1989","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1016\/S0028-3908(00)00075-7","article-title":"GABA-level increasing and anticonvulsant effects of three different GABA uptake inhibitors","volume":"39","author":"Dalby","year":"2000","journal-title":"Neuropharmacology"},{"key":"ref_15","first-page":"757","article-title":"New avenues for anti-epileptic drug discovery and development","volume":"20","author":"Klitgaard","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.eplepsyres.2015.01.001","article-title":"Progress report on new antiepileptic drugs: A summary of the Twelfth Eilat Conference (EILAT XII)","volume":"111","author":"Bialer","year":"2015","journal-title":"Epilepsy Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.pharmthera.2009.11.007","article-title":"Neuronal and non-neuronal GABA transporters as targets for antiepileptic drugs","volume":"125","author":"Madsen","year":"2010","journal-title":"Pharmacol. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"719","DOI":"10.2741\/e719","article-title":"Neuroprotective agents and modulation of temporal lobe epilepsy","volume":"7","author":"Fernandes","year":"2015","journal-title":"Front. Biosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s40409-015-0031-x","article-title":"Neuroactive compounds obtained from arthropod venoms as new therapeutic platforms for the treatment of neurological disorders","volume":"21","author":"Gomes","year":"2015","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1124\/mol.105.017319","article-title":"Neurochemical characterization of a neuroprotective compound from Parawixia bistriata spider venom that inhibits synaptosomal uptake of GABA and glycine","volume":"69","author":"Beleboni","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1076\/phbi.40.6.472.8436","article-title":"Anticonvulsant and GABA Uptake Inhibition Properties of Venom Fractions from the Spiders Parawixia bistriata and Scaptocosa raptoria","volume":"40","author":"Ribeiro","year":"2002","journal-title":"Pharm. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.brainres.2006.09.052","article-title":"Anticonvulsant and anxiolytic activity of FrPbAII, a novel GABA uptake inhibitor isolated from the venom of the social spider Parawixia bistriata (Araneidae: Araneae)","volume":"1124","author":"Liberato","year":"2006","journal-title":"Brain Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.lfs.2006.10.002","article-title":"Neuropharmacological profile of FrPbAII, purified from the venom of the social spider Parawixia bistriata (Araneae, Araneidae), in Wistar rats","volume":"80","author":"Gelfuso","year":"2007","journal-title":"Life Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.neulet.2013.02.074","article-title":"Parawixin2, a novel non-selective GABA uptake inhibitor from Parawixia bistriata spider venom, inhibits pentylenetetrazole-induced chemical kindling in rats","volume":"543","author":"Gelfuso","year":"2013","journal-title":"Neurosci. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0079-6123(02)35008-8","article-title":"Progression of neuronal damage after status epilepticus and during spontaneous seizures in a rat model of temporal lobe epilepsy","volume":"135","author":"Nissinen","year":"2002","journal-title":"Prog. Brain Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/0166-4328(83)90136-5","article-title":"Limbic seizures produced by pilocarpine in rats: Behavioural, electroencephalographic and neuropathological study","volume":"9","author":"Turski","year":"1983","journal-title":"Behav. Brain Res."},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1111\/j.0013-9580.2003.32803.x","article-title":"Therapy discovery for pharmacoresistant epilepsy and for disease-modifying therapeutics: summary of the NIH\/NINDS\/AES models II workshop","volume":"44","author":"Stables","year":"2003","journal-title":"Epilepsia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0920-1211(98)00092-8","article-title":"The course of untreated seizures in the pilocarpine model of epilepsy","volume":"34","author":"Arida","year":"1999","journal-title":"Epilepsy Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/0014-2999(95)00835-7","article-title":"Tiagabine prevents seizures, neuronal damage and memory impairment in experimental status epilepticus","volume":"299","author":"Halonen","year":"1996","journal-title":"Eur. J. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/0014-2999(91)90438-V","article-title":"Characterization of tiagabine (NO-328), a new potent and selective GABA uptake inhibitor","volume":"196","author":"Nielsen","year":"1991","journal-title":"Eur. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1006\/exnr.1994.1060","article-title":"Blockade of GABA uptake with tiagabine inhibits audiogenic seizures and reduces neuronal firing in the inferior colliculus of the genetically epilepsy-prone rat","volume":"126","author":"Faingold","year":"1994","journal-title":"Exp. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/0014-2999(94)00696-5","article-title":"The gamma-aminobutyric acid uptake inhibitor, tiagabine, is anticonvulsant in two animal models of reflex epilepsy","volume":"273","author":"Smith","year":"1995","journal-title":"Eur. J. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1111\/j.1528-1157.1995.tb02576.x","article-title":"A review of the preclinical pharmacology of tiagabine: a potent and selective anticonvulsant GABA uptake inhibitor","volume":"36","author":"Suzdak","year":"1995","journal-title":"Epilepsia"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1111\/j.1528-1157.1997.tb01478.x","article-title":"Antiepileptic effects of tiagabine, a selective GABA uptake inhibitor, in the rat kindling model of temporal lobe epilepsy","volume":"38","author":"Morimoto","year":"1997","journal-title":"Epilepsia"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/0006-8993(92)90433-A","article-title":"Protection against dendrotoxin-induced clonic seizures in mice by anticonvulsant drugs","volume":"575","author":"Coleman","year":"1992","journal-title":"Brain Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"11553","DOI":"10.1523\/JNEUROSCI.3362-05.2005","article-title":"GABAA receptor-mediated tonic inhibition in thalamic neurons","volume":"25","author":"Cope","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1124\/jpet.301.1.7","article-title":"Role of multidrug transporters in pharmacoresistance to antiepileptic drugs","volume":"301","author":"Potschka","year":"2002","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0304-3940(02)01193-X","article-title":"Neuroprotective effects of anticonvulsants in rat hippocampal slice cultures exposed to oxygen\/glucose deprivation","volume":"335","author":"Rekling","year":"2003","journal-title":"Neurosci. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S0006-8993(02)02871-8","article-title":"Neuroprotective effect of tiagabine in transient forebrain global ischemia: An in vivo microdialysis, behavioral, and histological study","volume":"946","author":"Iqbal","year":"2002","journal-title":"Brain Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0006-8993(00)02554-3","article-title":"Neuroprotective activity of tiagabine in a focal embolic model of cerebral ischemia","volume":"874","author":"Wang","year":"2000","journal-title":"Brain Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.nbd.2008.01.014","article-title":"Tiagabine is neuroprotective in the N171\u201382Q and R6\/2 mouse models of Huntington\u2019s disease","volume":"30","author":"Masuda","year":"2008","journal-title":"Neurobiol. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3109\/00207454.2010.530007","article-title":"Selective loss and axonal sprouting of GABAergic interneurons in the sclerotic hippocampus induced by LiCl-pilocarpine","volume":"121","author":"Long","year":"2011","journal-title":"Int. J. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.brainres.2008.07.097","article-title":"Time-course of neuronal death in the mouse pilocarpine model of chronic epilepsy using Fluoro-Jade C staining","volume":"1241","author":"Wang","year":"2008","journal-title":"Brain Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/S0306-4522(01)00446-8","article-title":"Preservation of perisomatic inhibitory input of granule cells in the epileptic human dentate gyrus","volume":"108","author":"Wittner","year":"2001","journal-title":"Neuroscience"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1113\/jphysiol.2007.146159","article-title":"Network hyperexcitability within the deep layers of the pilocarpine-treated rat entorhinal cortex","volume":"586","author":"Inaba","year":"2008","journal-title":"J. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1038\/ncomms2376","article-title":"On-demand optogenetic control of spontaneous seizures in temporal lobe epilepsy","volume":"4","author":"Armstrong","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0920-1211(95)00014-2","article-title":"The pathophysiologic relationships between lesion pathology, intracranial ictal EEG onsets, and hippocampal neuron losses in temporal lobe epilepsy","volume":"21","author":"Mathern","year":"1995","journal-title":"Epilepsy Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1093\/brain\/awh004","article-title":"Histopathology and reorganization of chandelier cells in the human epileptic sclerotic hippocampus","volume":"127","author":"Arellano","year":"2004","journal-title":"Brain"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1002\/hipo.1060","article-title":"Alterations of hippocampal GAbaergic system contribute to development of spontaneous recurrent seizures in the rat lithium-pilocarpine model of temporal lobe epilepsy","volume":"11","author":"Marescaux","year":"2001","journal-title":"Hippocampus"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1002\/cne.22235","article-title":"Initial loss but later excess of GABAergic synapses with dentate granule cells in a rat model of temporal lobe epilepsy","volume":"518","author":"Thind","year":"2010","journal-title":"J. Comp. Neurol."},{"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","first-page":"787","article-title":"Neuroprotective Properties of Topiramate in the Lithium- Pilocarpine Model of Epilepsy","volume":"308","author":"Rigoulot","year":"2004","journal-title":"Pharmacology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/0922-4106(94)90089-2","article-title":"Tiagabine, SK&F 89976-A, CI-966, and NNC-711 are selective for the cloned GABA transporter GAT-1","volume":"269","author":"Borden","year":"1994","journal-title":"Eur. J. Pharmacol."},{"key":"ref_55","unstructured":"Paxinos, G., and Watson, C. (1998). The Rat Brain in Stereotaxic Coordinates, Academic Press. [4th ed.]."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.brainres.2010.12.012","article-title":"Comparative neuroanatomical and temporal characterization of FluoroJade-positive neurodegeneration after status epilepticus induced by systemic and intrahippocampal pilocarpine in Wistar rats","volume":"1374","author":"Castro","year":"2011","journal-title":"Brain Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/cne.20482","article-title":"Effects of GABAergic transmissions on the immunoreactivities of calcium binding proteins in the gerbil hippocampus","volume":"485","author":"Kwak","year":"2005","journal-title":"J. Comp. Neurol."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/9\/9\/262\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:43:17Z","timestamp":1760208197000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/9\/9\/262"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,25]]},"references-count":57,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2017,9]]}},"alternative-id":["toxins9090262"],"URL":"https:\/\/doi.org\/10.3390\/toxins9090262","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,25]]}}}