{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T11:37:36Z","timestamp":1763552256052,"version":"build-2065373602"},"reference-count":121,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Secretar\u00eda de Investigaci\u00f3n y Posgrado\u2014Instituto Polit\u00e9cnico Nacional","award":["SIP-IPN 20181089","SIP-IPN 20190023"],"award-info":[{"award-number":["SIP-IPN 20181089","SIP-IPN 20190023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Thalidomide (TAL) has shown potential therapeutic effects in neurological diseases like epilepsy. Both clinical and preclinical studies show that TAL may act as an antiepileptic drug and as a possible treatment against disease development. However, the evidence for these effects is limited. Therefore, the antiepileptogenic and anti-inflammatory effects of TAL were evaluated herein. Sprague Dawley male rats were randomly allocated to one of five groups (n = 18 per group): control (C); status epilepticus (SE); SE-TAL (25 mg\/kg); SE-TAL (50 mg\/kg); and SE-topiramate (TOP; 60mg\/kg). The lithium-pilocarpine model was used, and one day after SE induction the rats received pharmacological treatment for one week. The brain was obtained, and the hippocampus was micro-dissected 8, 18, and 28 days after SE. TNF-\u03b1, IL-6, and IL-1\u03b2 concentrations were quantified. TOP and TAL (50 mg\/kg) increased the latency to the first of many spontaneous recurrent seizures (SRS) and decreased SRS frequency, as well as decreasing TNF-\u03b1 and IL-1\u03b2 concentrations in the hippocampus. In conclusion, the results showed that both TAL (50 mg\/kg) and TOP have anti-ictogenic and antiepileptogenic effects, possibly by decreasing neuroinflammation.<\/jats:p>","DOI":"10.3390\/ijms24076488","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T04:45:35Z","timestamp":1680151535000},"page":"6488","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Thalidomide Attenuates Epileptogenesis and Seizures by Decreasing Brain Inflammation in Lithium Pilocarpine Rat Model"],"prefix":"10.3390","volume":"24","author":[{"given":"Ir\u00e1n M.","family":"Cumbres-Vargas","sequence":"first","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Mexico City 07738, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio R.","family":"Zamudio","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Mexico City 07738, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luz A.","family":"Pichardo-Mac\u00edas","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Mexico City 07738, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Ram\u00edrez-San Juan","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Mexico City 07738, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1177\/107385840100700410","article-title":"Mesial Temporal Lobe Epilepsy: What Have We Learned?","volume":"7","author":"Engel","year":"2001","journal-title":"Neuroscientist"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/epi.16423","article-title":"Impaired vigilance networks in temporal lobe epilepsy: Mechanisms and clinical implications","volume":"61","author":"Englot","year":"2020","journal-title":"Epilepsia"},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1097\/WNP.0b013e31826b3ab7","article-title":"Mesial Temporal Lobe Epilepsy","volume":"29","author":"Tatum","year":"2012","journal-title":"J. Clin. Neurophysiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1590\/S0001-37652009000300003","article-title":"The pilocarpine model of epilepsy: What have we learned?","volume":"81","author":"Scorza","year":"2009","journal-title":"An. Acad. Bras. Cienc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"18024","DOI":"10.1038\/nrdp.2018.24","article-title":"Epilepsy","volume":"4","author":"Devinsky","year":"2018","journal-title":"Nat. Rev. Dis. Prim."},{"unstructured":"World Health Organization (2023, January 20). Epilepsy. WHO Newsroom. Available online: https:\/\/www.who.int\/health-topics\/epilepsy#tab=tab_1.","key":"ref_7"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1074537","DOI":"10.3389\/fcell.2022.1074537","article-title":"Editorial: Neuroinflammation in acquired epilepsy","volume":"10","author":"Jiang","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"doi-asserted-by":"crossref","unstructured":"Chen, Y., Nagib, M.M., Yasmen, N., Sluter, M.N., Littlejohn, T.L., Yu, Y., and Jiang, J. (2023). Neuroinflammatory mediators in acquired epilepsy: An update. Inflamm. Res., 1\u201319.","key":"ref_9","DOI":"10.1007\/s00011-023-01700-8"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1002\/epi4.12490","article-title":"Antiepileptogenesis and disease modification: Progress, challenges, and the path forward\u2014Report of the Preclinical Working Group of the 2018 NINDS-sponsored antiepileptogenesis and disease modification workshop","volume":"6","author":"Galanopoulou","year":"2021","journal-title":"Epilepsia Open"},{"doi-asserted-by":"crossref","unstructured":"Afrikanova, T., Serruys, A.-S.K., Buenafe, O.E.M., Clinckers, R., Smolders, I., de Witte, P.A., Crawford, A.D., and Esguerra, C.V. (2013). Validation of the Zebrafish Pentylenetetrazol Seizure Model: Locomotor versus Electrographic Responses to Antiepileptic Drugs. PLoS ONE, 8.","key":"ref_11","DOI":"10.1371\/journal.pone.0054166"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1146\/annurev-pharmtox-010814-124607","article-title":"Candidate Drug Targets for Prevention or Modification of Epilepsy","volume":"55","author":"Varvel","year":"2015","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"108055","DOI":"10.1016\/j.neuropharm.2020.108055","article-title":"The feast and famine: Epilepsy treatment and treatment gaps in early 21st century","volume":"170","author":"Klein","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s13311-014-0257-2","article-title":"Past and Present Definitions of Epileptogenesis and Its Biomarkers","volume":"11","author":"Engel","year":"2014","journal-title":"Neurotherapeutics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nrn3482","article-title":"Mechanisms of epileptogenesis: A convergence on neural circuit dysfunction","volume":"14","author":"Goldberg","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1002\/ana.410340604","article-title":"Characteristics of medial temporal lobe epilepsy: I. Results of history and physical examination","volume":"34","author":"French","year":"1993","journal-title":"Ann. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jneumeth.2015.03.009","article-title":"Animal models of temporal lobe epilepsy following systemic chemoconvulsant administration","volume":"260","author":"Avoli","year":"2016","journal-title":"J. Neurosci. Methods"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.neubiorev.2021.08.020","article-title":"The pilocarpine model of mesial temporal lobe epilepsy: Over one decade later, with more rodent species and new investigative approaches","volume":"130","author":"Biagini","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_19","first-page":"107605","article-title":"The holy grail of epilepsy prevention: Preclinical approaches to antiepileptogenic treatments","volume":"167","year":"2019","journal-title":"Neuropharmacology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1111\/epi.16450","article-title":"Repurposed molecules for antiepileptogenesis: Missing an opportunity to prevent epilepsy?","volume":"61","author":"Klein","year":"2020","journal-title":"Epilepsia"},{"doi-asserted-by":"crossref","unstructured":"Wolinski, P., Ksiazek-Winiarek, D., and Glabinski, A. (2022). Cytokines and Neurodegeneration in Epileptogenesis. Brain Sci., 12.","key":"ref_21","DOI":"10.3390\/brainsci12030380"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"781174","DOI":"10.3389\/fnagi.2021.781174","article-title":"Inflammation Mediated Epileptogenesis as Possible Mechanism Underlying Ischemic Post-stroke Epilepsy","volume":"13","author":"Gruber","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"108044","DOI":"10.1016\/j.neuropharm.2020.108044","article-title":"Seizure-induced neuroinflammation contributes to ectopic neurogenesis and aggressive behavior in pilocarpine-induced status epilepticus mice","volume":"170","author":"Zhu","year":"2020","journal-title":"Neuropharmacology"},{"doi-asserted-by":"crossref","unstructured":"Sokolova, T.V., Zabrodskaya, Y.M., Litovchenko, A.V., Paramonova, N.M., Kasumov, V.R., Kravtsova, S.V., Skiteva, E.N., Sitovskaya, D.A., and Bazhanova, E.D. (2022). Relationship between Neuroglial Apoptosis and Neuroinflammation in the Epileptic Focus of the Brain and in the Blood of Patients with Drug-Resistant Epilepsy. Int. J. Mol. Sci., 23.","key":"ref_24","DOI":"10.3390\/ijms232012561"},{"doi-asserted-by":"crossref","unstructured":"\u0141ukasiuk, K., and Laso\u0144, W. (2023). Emerging Molecular Targets for Anti-Epileptogenic and Epilepsy Modifying Drugs. Int. J. Mol. Sci., 24.","key":"ref_25","DOI":"10.3390\/ijms24032928"},{"doi-asserted-by":"crossref","unstructured":"Contreras-Garc\u00eda, I.J., C\u00e1rdenas-Rodr\u00edguez, N., Romo-Mancillas, A., Bandala, C., Zamudio, S.R., G\u00f3mez-Manzo, S., Hern\u00e1ndez-Ochoa, B., Mendoza-Torreblanca, J.G., and Pichardo-Mac\u00edas, L.A. (2022). Levetiracetam Mechanisms of Action: From Molecules to Systems. Pharmaceuticals, 15.","key":"ref_26","DOI":"10.3390\/ph15040475"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.eplepsyres.2011.04.008","article-title":"Strong anticonvulsant effect of thalidomide on amygdaloid kindling","volume":"95","author":"Palencia","year":"2011","journal-title":"Epilepsy Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4082","DOI":"10.1073\/pnas.91.9.4082","article-title":"Thalidomide is an inhibitor of angiogenesis","volume":"91","author":"Loughnan","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1002\/cpt196563303","article-title":"Thalidomide in the treatment of lepra reactions","volume":"6","author":"Sheskin","year":"1965","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/j.biocel.2007.01.022","article-title":"The thalidomide saga","volume":"39","author":"Melchert","year":"2007","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jns.2007.03.010","article-title":"Thalidomide inhibits pentylenetetrazole-induced seizures","volume":"258","author":"Palencia","year":"2007","journal-title":"J. Neurol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"671","DOI":"10.2131\/jts.43.671","article-title":"Thalidomide protects against acute pentylenetetrazol and pilocarpine-induced seizures in mice","volume":"43","author":"Juan","year":"2018","journal-title":"J. Toxicol. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.eplepsyres.2010.10.003","article-title":"Thalidomide for treatment of refractory epilepsy","volume":"92","author":"Palencia","year":"2010","journal-title":"Epilepsy Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2644","DOI":"10.4049\/jimmunol.168.6.2644","article-title":"Thalidomide Suppresses NF-\u03baB Activation Induced by TNF and H2O2, But Not That Activated by Ceramide, Lipopolysaccharides, or Phorbol Ester","volume":"168","author":"Majumdar","year":"2002","journal-title":"J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.2174\/156802612801784443","article-title":"TNF \u03b1 Signaling Beholds Thalidomide Saga: A Review of Mechanistic Role of TNF-\u03b1 Signaling Under Thalidomide","volume":"12","author":"Majumder","year":"2012","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.yebeh.2014.03.020","article-title":"Nitric oxide mediates the anticonvulsant effects of thalidomide on pentylenetetrazole-induced clonic seizures in mice","volume":"34","author":"Payandemehr","year":"2014","journal-title":"Epilepsy Behav."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6","DOI":"10.14581\/jer.21002","article-title":"Effect of Lenalidomide on Pentylenetetrazole-Induced Clonic Seizure Threshold in Mice: A Role for N-Methyl-D-Aspartic Acid Receptor\/Nitric Oxide Pathway","volume":"11","author":"Dafe","year":"2021","journal-title":"J. Epilepsy Res."},{"key":"ref_38","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_39","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":"2010","journal-title":"Nat. Rev. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.tins.2012.11.008","article-title":"Glia and epilepsy: Excitability and inflammation","volume":"36","author":"Devinsky","year":"2013","journal-title":"Trends Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1016\/j.bbadis.2019.01.026","article-title":"Excitotoxicity, neuroinflammation and oxidant stress as molecular bases of epileptogenesis and epilepsy-derived neurodegeneration: The role of vitamin E","volume":"1865","author":"Ambrogini","year":"2019","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Basis Dis."},{"doi-asserted-by":"crossref","unstructured":"Sanz, P., and Garcia-Gimeno, M.A. (2020). Reactive Glia Inflammatory Signaling Pathways and Epilepsy. Int. J. Mol. Sci., 21.","key":"ref_42","DOI":"10.3390\/ijms21114096"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0887-8994(03)00216-9","article-title":"Rasmussen syndrome and long-term response to thalidomide","volume":"29","author":"Marjanovic","year":"2003","journal-title":"Pediatr. Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"106362","DOI":"10.1016\/j.eplepsyres.2020.106362","article-title":"Anticonvulsant Effects of Thalidomide on Pentylenetetrazole-Induced Seizure in Mice: A Role for Opioidergic and Nitrergic Transmissions","volume":"164","author":"Pourshadi","year":"2020","journal-title":"Epilepsy Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"586","DOI":"10.4103\/1735-5362.327505","article-title":"Anticonvulsive evaluation and histopathological survey of thalidomide synthetic analogs on lithium-pilocarpine-induced status epilepticus in rats","volume":"16","author":"Mortazavi","year":"2021","journal-title":"Res. Pharm. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.brainres.2010.08.007","article-title":"PI3K\/Akt signaling pathway is required for neuroprotection of thalidomide on hypoxic\u2013ischemic cortical neurons in vitro","volume":"1357","author":"Zhang","year":"2010","journal-title":"Brain Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1080\/10406638.2020.1776345","article-title":"Synthesis and Evaluation of Anti-Epileptic Properties of New Phthalimide-4,5-Dihydrothiazole-Amide Derivatives","volume":"42","author":"Rafiei","year":"2020","journal-title":"Polycycl. Aromat. Compd."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"534","DOI":"10.4103\/1735-5362.272562","article-title":"Synthesis, molecular docking, and antiepileptic activity of novel phthalimide derivatives bearing amino acid conjugated anilines","volume":"14","author":"Amanlou","year":"2019","journal-title":"Res. Pharm. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s11064-014-1504-y","article-title":"Role for Pro-inflammatory Cytokines in Regulating Expression of GABA Transporter Type 1 and 3 in Specific Brain Regions of Kainic Acid-Induced Status Epilepticus","volume":"40","author":"Su","year":"2015","journal-title":"Neurochem. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.molmed.2018.12.001","article-title":"TNF\u03b1-Driven Astrocyte Purinergic Signaling during Epileptogenesis","volume":"25","author":"Bedner","year":"2019","journal-title":"Trends Mol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1002\/glia.23519","article-title":"Blocking TNF\u03b1-driven astrocyte purinergic signaling restores normal synaptic activity during epileptogenesis","volume":"66","author":"Nikolic","year":"2018","journal-title":"Glia"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"21362","DOI":"10.1074\/jbc.M600504200","article-title":"Tumor Necrosis Factor-\u03b1 Induces Neurotoxicity via Glutamate Release from Hemichannels of Activated Microglia in an Autocrine Manner","volume":"281","author":"Takeuchi","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"759","DOI":"10.2174\/1570159X14666160603115942","article-title":"Gap Junction Blockers: An Overview of their Effects on Induced Seizures in Animal Models","volume":"14","year":"2016","journal-title":"Curr. Neuropharmacol."},{"doi-asserted-by":"crossref","unstructured":"Volnova, A., Tsytsarev, V., Ganina, O., V\u00e9lez-Crespo, G.E., Alves, J.M., Ignashchenkova, A., and Inyushin, M. (2022). The Anti-Epileptic Effects of Carbenoxolone In Vitro and In Vivo. Int. J. Mol. Sci., 23.","key":"ref_54","DOI":"10.3390\/ijms23020663"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.biopha.2018.10.068","article-title":"Targeting gap junction in epilepsy: Perspectives and challenges","volume":"109","author":"Li","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/S0006-2952(01)00751-1","article-title":"Stimulation of gap junctional intercellular communication by thalidomide and thalidomide analogs in human fetal skin fibroblasts (HFFF2) and in rat liver epithelial cells (WB-F344)","volume":"62","author":"Onat","year":"2001","journal-title":"Biochem. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1016\/S0006-2952(97)00096-8","article-title":"Stimulation of gap junctional intercellular communication by thalidomide and thalidomide analogs in human skin fibroblasts","volume":"53","author":"Nicolai","year":"1997","journal-title":"Biochem. Pharmacol."},{"doi-asserted-by":"crossref","unstructured":"Rho, J.M., Sankar, R., and Stafstrom, C.E. (2010). Epilepsy Mechanisms, Models and Traslational Perspectives, CRC Press Taylor and Francis Group. [1st ed.].","key":"ref_58","DOI":"10.1201\/9781420085594"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1021\/acsptsci.1c00042","article-title":"N-Adamantyl Phthalimidine: A New Thalidomide-like Drug That Lacks Cereblon Binding and Mitigates Neuronal and Synaptic Loss, Neuroinflammation, and Behavioral Deficits in Traumatic Brain Injury and LPS Challenge","volume":"4","author":"Hsueh","year":"2021","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.2174\/0929867324666170601074646","article-title":"A Mini-Review on Thalidomide: Chemistry, Mechanisms of Action, Therapeutic Potential and Anti-Angiogenic Properties in Multiple Myeloma","volume":"24","author":"Mercurio","year":"2017","journal-title":"Curr. Med. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.euroneuro.2008.06.008","article-title":"Experimentally induced various inflammatory models and seizure: Understanding the role of cytokine in rat","volume":"18","author":"Rao","year":"2008","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1084\/jem.173.3.699","article-title":"Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes","volume":"173","author":"Sampaio","year":"1991","journal-title":"J. Exp. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1080\/08923970802135161","article-title":"Thalidomide Suppressed IL-1\u03b2 While Enhancing TNF-\u03b1 and IL-10, When Cells in Whole Blood were Stimulated with Lipopolysaccharide","volume":"30","author":"Shannon","year":"2008","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1084\/jem.177.6.1675","article-title":"Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation","volume":"177","author":"Moreira","year":"1993","journal-title":"J. Exp. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5222","DOI":"10.1021\/jm030152f","article-title":"Thiothalidomides: Novel Isosteric Analogues of Thalidomide with Enhanced TNF-\u03b1 Inhibitory Activity","volume":"46","author":"Zhu","year":"2003","journal-title":"J. Med. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"22382","DOI":"10.1074\/jbc.M100938200","article-title":"Inhibition of NF-\u03baB Activity by Thalidomide through Suppression of I\u03baB Kinase Activity","volume":"276","author":"Keifer","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_67","first-page":"33","article-title":"Thalidomide inhibits lipopolysaccharide-induced tumor necrosis factor-\u03b1 production via down-regulation of MyD88 expression","volume":"15","author":"Noman","year":"2009","journal-title":"J. Endotoxin Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0002-9440(10)64714-1","article-title":"Thalidomide Inhibits Angiogenesis in Embryoid Bodies by the Generation of Hydroxyl Radicals","volume":"156","author":"Sauer","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"7552","DOI":"10.1073\/pnas.93.15.7552","article-title":"Binding of thalidomide to alpha1-acid glycoprotein may be involved in its inhibition of tumor necrosis factor alpha production","volume":"93","author":"Turk","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1038\/leu.2012.119","article-title":"Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide","volume":"26","author":"Mendy","year":"2012","journal-title":"Leukemia"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"9130608","DOI":"10.1155\/2017\/9130608","article-title":"Cereblon: A Protein Crucial to the Multiple Functions of Immunomodulatory Drugs as well as Cell Metabolism and Disease Generation","volume":"2017","author":"Shi","year":"2017","journal-title":"J. Immunol. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1111\/bjh.12708","article-title":"Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors I karos and A iolos via modulation of the E 3 ubiquitin ligase complex CRL4(CRBN.)","volume":"164","author":"Gandhi","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"656921","DOI":"10.3389\/fnins.2021.656921","article-title":"Repurposing Immunomodulatory Imide Drugs (IMiDs) in Neuropsychiatric and Neurodegenerative Disorders","volume":"15","author":"Jung","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"484","DOI":"10.5483\/BMBRep.2020.53.9.119","article-title":"Susceptibility of pentylenetetrazole-induced seizures in mice with Cereblon gene knockout","volume":"53","author":"Jeon","year":"2020","journal-title":"BMB Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"8692","DOI":"10.1523\/JNEUROSCI.23-25-08692.2003","article-title":"Interleukin-1\u03b2 Enhances NMDA Receptor-Mediated Intracellular Calcium Increase through Activation of the Src Family of Kinases","volume":"23","author":"Viviani","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/S0306-4522(98)00680-0","article-title":"Interleukin-1\u03b2 activates forebrain glial cells and increases nitric oxide production and cortical glutamate and GABA release in vivo: Implications for Alzheimer\u2019s disease","volume":"91","author":"Casamenti","year":"1999","journal-title":"Neuroscience"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1159\/000026433","article-title":"Cytokine Effects on Glutamate Uptake by Human Astrocytes","volume":"7","author":"Hu","year":"2000","journal-title":"Neuroimmunomodulation"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/89490","article-title":"CXCR4-activated astrocyte glutamate release via TNF\u03b1: Amplification by microglia triggers neurotoxicity","volume":"4","author":"Bezzi","year":"2001","journal-title":"Nat. Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1038\/nm1277","article-title":"An astrocytic basis of epilepsy","volume":"11","author":"Tian","year":"2005","journal-title":"Nat. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"9312","DOI":"10.1523\/JNEUROSCI.2836-06.2006","article-title":"Astrocytic Glutamate Is Not Necessary for the Generation of Epileptiform Neuronal Activity in Hippocampal Slices","volume":"26","author":"Fellin","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_81","first-page":"521","article-title":"Blood-brain barrier leakage may lead to progression of temporal lobe epilepsy","volume":"130","author":"Araujo","year":"2006","journal-title":"Brain"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.nbd.2015.07.003","article-title":"GABAA currents are decreased by IL-1\u03b2 in epileptogenic tissue of patients with temporal lobe epilepsy: Implications for ictogenesis","volume":"82","author":"Roseti","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/S0006-8993(97)00787-7","article-title":"Interleukin-1\u03b2 does not increase synaptic inhibition in hippocampal CA3 pyramidal and dentate gyrus granule cells of the rat in vitro","volume":"768","author":"Zeise","year":"1997","journal-title":"Brain Res."},{"key":"ref_84","first-page":"497","article-title":"Interleukin-1beta inhibits gamma-aminobutyric acid type A (GABA(A)) receptor cur-rent in cultured hippocampal neurons","volume":"292","author":"Wang","year":"2000","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3256","DOI":"10.1093\/brain\/awn271","article-title":"A novel non-transcriptional pathway mediates the proconvulsive effects of interleukin-1","volume":"131","author":"Balosso","year":"2008","journal-title":"Brain"},{"doi-asserted-by":"crossref","unstructured":"Guzzo, E.F.M., Rosa, G.D.L., Domingues, A.M., Padilha, R.B., and Coitinho, A.S. Reduction of seizures and inflammatory markers by betamethasone in a kindling seizure model. Steroids, 2023.","key":"ref_86","DOI":"10.1016\/j.steroids.2023.109202"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.seizure.2015.01.009","article-title":"IL-1\u03b2, IL-6 and IL1Ra levels in temporal lobe epilepsy","volume":"26","author":"Uludag","year":"2015","journal-title":"Seizure"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"708","DOI":"10.4049\/jimmunol.179.1.708","article-title":"Thalidomide Prevents Bleomycin-Induced Pulmonary Fibrosis in Mice","volume":"179","author":"Tabata","year":"2007","journal-title":"J. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"811","DOI":"10.2147\/NDT.S512","article-title":"Topiramate in the treatment of partial and generalized epilepsy","volume":"3","author":"Faught","year":"2008","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1001\/archinte.165.14.1600","article-title":"Use of Oral Topiramate to Promote Smoking Abstinence Among Alcohol-Dependent Smokers","volume":"165","author":"Johnson","year":"2005","journal-title":"Arch. Intern. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1111\/j.1369-1600.2012.00499.x","article-title":"Topiramate\u2019s effects on cocaine induced subjective mood, craving and preference for money over drug taking","volume":"18","author":"Johnson","year":"2013","journal-title":"Addict. Boil."},{"doi-asserted-by":"crossref","unstructured":"Wiffen, P.J., Derry, S., Lunn, M.P., and Moore, R.A. (2013). Topiramate for neuropathic pain and fibromyalgia in adults. Cochrane Database Syst. Rev.","key":"ref_92","DOI":"10.1002\/14651858.CD008314.pub3"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s40122-022-00452-3","article-title":"Effectiveness and Safety of Chronic Migraine Preventive Treatments: A Systematic Literature Review","volume":"12","author":"Blumenfeld","year":"2022","journal-title":"Pain Ther."},{"key":"ref_94","first-page":"15","article-title":"Topiramate is both neuroprotective and antiepileptogenic in the pilocarpine model of status epilepticus","volume":"43","author":"DeLorenzo","year":"2002","journal-title":"Epilepsia"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1203\/01.pdr.0000196333.16608.30","article-title":"Treatment of Experimental Status Epilepticus in Immature Rats: Dissociation Between Anticonvulsant and Antiepileptogenic Effects","volume":"59","author":"Suchomelova","year":"2006","journal-title":"Pediatr. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"108802","DOI":"10.1016\/j.yebeh.2022.108802","article-title":"The anticonvulsant effect of chronic treatment with topiramate after pilocarpine-induced status epilepticus is accompanied by a suppression of comorbid behavioral impairments and robust neuroprotection in limbic regions in rats","volume":"134","author":"Atanasova","year":"2022","journal-title":"Epilepsy Behav."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1111\/j.1528-1167.2007.00987.x","article-title":"Age-dependent Effects of Topiramate on the Acquisition and the Retention of Rapid Kindling","volume":"48","author":"Mazarati","year":"2007","journal-title":"Epilepsia"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0304-3940(97)00543-0","article-title":"Topiramate attenuates voltage-gated sodium currents in rat cerebellar granule cells","volume":"231","author":"Zona","year":"1997","journal-title":"Neurosci. Lett."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1528-1157.2000.tb02165.x","article-title":"Topiramate modulates GABA-evoked currents in murine cortical neurons by a nonbenzodiazepine mechanism","volume":"41","author":"White","year":"2000","journal-title":"Epilepsia"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/j.1528-1157.2000.tb02164.x","article-title":"Cellular Actions of Topiramate: Blockade of Kainate-Evoked Inward Currents in Cultured Hippocampal Neurons","volume":"41","author":"Gibbs","year":"2000","journal-title":"Epilepsia"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s00213-009-1683-4","article-title":"Effect of topiramate treatment on ethanol consumption in rats","volume":"207","author":"Breslin","year":"2009","journal-title":"Psychopharmacology"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/B978-0-12-801284-0.00012-9","article-title":"Opportunities for the Development of Neuroimmune Therapies in Addiction","volume":"118","author":"Ray","year":"2014","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1016\/j.jpsychires.2013.07.026","article-title":"Impact of mood stabilizers and antiepileptic drugs on cytokine production in-vitro","volume":"47","author":"Himmerich","year":"2013","journal-title":"J. Psychiatr. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.eplepsyres.2016.09.020","article-title":"The effects of topiramate on lipopolysaccharide (LPS)-induced proinflammatory cytokine release from primary rat microglial cell cultures","volume":"127","author":"Andrzejczak","year":"2016","journal-title":"Epilepsy Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1002\/glia.20830","article-title":"Sodium channel activity modulates multiple functions in microglia","volume":"57","author":"Black","year":"2009","journal-title":"Glia"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.fct.2018.05.022","article-title":"Topiramate mitigates 3-nitropropionic acid-induced striatal neurotoxicity via modulation of AMPA receptors","volume":"118","author":"Shalaby","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/s12640-016-9695-4","article-title":"Topiramate Confers Neuroprotection Against Methylphenidate-Induced Neurodegeneration in Dentate Gyrus and CA1 Regions of Hippocampus via CREB\/BDNF Pathway in Rats","volume":"31","author":"Motaghinejad","year":"2017","journal-title":"Neurotox. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.bbi.2008.03.009","article-title":"The role of cytokines in the pathophysiology of epilepsy","volume":"22","author":"Vezzani","year":"2008","journal-title":"Brain, Behav. Immun."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.expneurol.2011.09.033","article-title":"Epilepsy and brain inflammation","volume":"244","author":"Vezzani","year":"2011","journal-title":"Exp. Neurol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.neuropharm.2012.04.004","article-title":"The role of inflammation in epileptogenesis","volume":"69","author":"Vezzani","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.tips.2016.03.001","article-title":"Anti-Inflammatory Small Molecules to Treat Seizures and Epilepsy: From Bench to Bedside","volume":"37","author":"Dey","year":"2016","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-016-0786-1","article-title":"Inflammation in epileptogenesis after traumatic brain injury","volume":"14","author":"Webster","year":"2017","journal-title":"J. Neuroinflammation"},{"doi-asserted-by":"crossref","unstructured":"Abraham, A., Bustos, J.A., Carabin, H., de Meijere, R., Sahu, P.S., Rajshekhar, V., Singh, G., White, A.C., Chiodini, P.L., and Gabri\u00ebl, S. (2021). The effectiveness of anti-inflammatory and anti-seizure medication for individuals with single enhancing lesion neurocysticercosis: A meta-analysis and expert group-based consensus recommendations. PLoS Neglected Trop. Dis., 15.","key":"ref_113","DOI":"10.1371\/journal.pntd.0009193"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.eplepsyres.2018.01.004","article-title":"Effect of levetiracetam on extracellular amino acid levels in the dorsal hippocampus of rats with temporal lobe epilepsy","volume":"140","author":"Adriana","year":"2018","journal-title":"Epilepsy Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.yebeh.2019.05.025","article-title":"Subchronic cerebrolysin treatment alleviates cognitive impairments and dendritic arborization alterations of granular neurons in the hippocampal dentate gyrus of rats with temporal lobe epilepsy","volume":"97","author":"Zamudio","year":"2019","journal-title":"Epilepsy Behav."},{"doi-asserted-by":"crossref","unstructured":"Modebadze, T., Morgan, N.H., P\u00e9r\u00e8s, I.A.A., Hadid, R.D., Amada, N., Hill, C., Williams, C., Stanford, I.M., Morris, C.M., and Jones, R.S.G. (2016). A Low Mortality, High Morbidity Reduced Intensity Status Epilepticus (RISE) Model of Epilepsy and Epileptogenesis in the Rat. PLoS ONE, 11.","key":"ref_116","DOI":"10.1371\/journal.pone.0147265"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e04557","DOI":"10.1016\/j.heliyon.2020.e04557","article-title":"The evolution of the pilocarpine animal model of status epilepticus","volume":"6","author":"Juvale","year":"2020","journal-title":"Heliyon"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0920-1211(01)00272-8","article-title":"Repeated low-dose treatment of rats with pilocarpine: Low mortality but high proportion of rats developing epilepsy","volume":"46","author":"Glien","year":"2001","journal-title":"Epilepsy Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.expneurol.2007.03.008","article-title":"Cyclicity of spontaneous recurrent seizures in pilocarpine model of temporal lobe epilepsy in rat","volume":"205","author":"Goffin","year":"2007","journal-title":"Exp. Neurol."},{"doi-asserted-by":"crossref","unstructured":"Sultan, F. (2013). Dissection of Different Areas from Mouse Hippocampus. Bio-Protocol, 3.","key":"ref_120","DOI":"10.21769\/BioProtoc.955"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/0003-2697(85)90442-7","article-title":"Measurement of protein using bicinchoninic acid","volume":"150","author":"Smith","year":"1985","journal-title":"Anal. Biochem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/7\/6488\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:06:57Z","timestamp":1760123217000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/7\/6488"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,30]]},"references-count":121,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ijms24076488"],"URL":"https:\/\/doi.org\/10.3390\/ijms24076488","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2023,3,30]]}}}