{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T04:42:39Z","timestamp":1793421759320,"version":"4.5.0"},"reference-count":70,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100008273","name":"Novartis Foundation","doi-asserted-by":"publisher","award":["14B095"],"award-info":[{"award-number":["14B095"]}],"id":[{"id":"10.13039\/100008273","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030_189065"],"award-info":[{"award-number":["310030_189065"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001605","name":"Epilepsy Foundation","doi-asserted-by":"publisher","award":["37213.1 IP-LS"],"award-info":[{"award-number":["37213.1 IP-LS"]}],"id":[{"id":"10.13039\/100001605","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neuropharmacology"],"published-print":{"date-parts":[[2020,12]]},"DOI":"10.1016\/j.neuropharm.2020.108297","type":"journal-article","created":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T20:54:15Z","timestamp":1599080055000},"page":"108297","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":33,"special_numbering":"C","title":["Novel brain permeant mTORC1\/2 inhibitors are as efficacious as rapamycin or everolimus in mouse models of acquired partial epilepsy and tuberous sclerosis complex"],"prefix":"10.1016","volume":"180","author":[{"given":"Wiebke","family":"Theilmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birthe","family":"Gericke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Schidlitzki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Muhammad","family":"Muneeb Anjum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"Borsdorf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timon","family":"Harries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven L.","family":"Roberds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean J.","family":"Aguiar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Brunner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven C.","family":"Leiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dekun","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doriano","family":"Fabbro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Hillmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias P.","family":"Wymann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"L\u00f6scher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.neuropharm.2020.108297_bib1","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1002\/ana.23943","article-title":"TORC1-dependent epilepsy caused by acute biallelic Tsc1 deletion in adult mice","volume":"74","author":"Abs","year":"2013","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.neuropharm.2020.108297_bib2","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.yebeh.2018.09.016","article-title":"Automated quantification of EEG spikes and spike clusters as a new read out in Theiler's virus mouse model of encephalitis-induced epilepsy","volume":"88","author":"Anjum","year":"2018","journal-title":"Epilepsy Behav."},{"key":"10.1016\/j.neuropharm.2020.108297_bib3","doi-asserted-by":"crossref","first-page":"539","DOI":"10.7164\/antibiotics.31.539","article-title":"Rapamycin (AY-22,989), a new antifungal antibiotic. III. In vitro and in vivo evaluation","volume":"31","author":"Baker","year":"1978","journal-title":"J. Antibiot. (Tokyo)"},{"key":"10.1016\/j.neuropharm.2020.108297_bib4","doi-asserted-by":"crossref","first-page":"7254","DOI":"10.1021\/acs.jmedchem.7b00930","article-title":"5-(4,6-Dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine (PQR309), a potent, brain-penetrant, orally bioavailable, pan-class I PI3K\/mTOR inhibitor as clinical candidate in oncology","volume":"60","author":"Beaufils","year":"2017","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.neuropharm.2020.108297_bib5","doi-asserted-by":"crossref","first-page":"14683","DOI":"10.1038\/ncomms14683","article-title":"Deconvolution of Buparlisib's mechanism of action defines specific PI3K and tubulin inhibitors for therapeutic intervention","volume":"8","author":"Bohnacker","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.neuropharm.2020.108297_bib6","doi-asserted-by":"crossref","DOI":"10.1021\/acs.jmedchem.0c00620","article-title":"4-(Difluoromethyl)-5-(4-((3R,5S)-3,5-dimethylmorpholino)-6-((R)-3-methylmorpholino)-1,3,5-triazin-2-yl)pyridin-2-amine (PQR626), a potent, orally available, and brain-penetrant mTOR inhibitor for the treatment of neurological disorders","author":"Borsari","year":"2020","journal-title":"J. Med. Chem. submitted."},{"key":"10.1016\/j.neuropharm.2020.108297_bib7","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S0306-4522(98)00401-1","article-title":"Recurrent seizures and hippocampal sclerosis following intrahippocampal kainate injection in adult mice: electroencephalography, histopathology and synaptic reorganization similar to mesial temporal lobe epilepsy","volume":"89","author":"Bouilleret","year":"1999","journal-title":"Neuroscience"},{"key":"10.1016\/j.neuropharm.2020.108297_bib8","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.neuropharm.2018.08.002","article-title":"The novel, catalytic mTORC1\/2 inhibitor PQR620 and the PI3K\/mTORC1\/2 inhibitor PQR530 effectively cross the blood-brain barrier and increase seizure threshold in a mouse model of chronic epilepsy","volume":"140","author":"Brandt","year":"2018","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.neuropharm.2020.108297_bib9","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0057808","article-title":"Rapamycin reverses status epilepticus-induced memory deficits and dendritic damage","volume":"8","author":"Brewster","year":"2013","journal-title":"PloS One"},{"key":"10.1016\/j.neuropharm.2020.108297_bib10","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1523\/JNEUROSCI.4852-10.2011","article-title":"Rapamycin suppresses mossy fiber sprouting but not seizure frequency in a mouse model of temporal lobe epilepsy","volume":"31","author":"Buckmaster","year":"2011","journal-title":"J. Neurosci."},{"key":"10.1016\/j.neuropharm.2020.108297_bib11","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1038\/s41591-019-0608-y","article-title":"Therapeutic inhibition of mTORC2 rescues the behavioral and neurophysiological abnormalities associated with Pten-deficiency","volume":"25","author":"Chen","year":"2019","journal-title":"Nat. Med."},{"key":"10.1016\/j.neuropharm.2020.108297_bib12","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1038\/ng1665","article-title":"The origins and uses of mouse outbred stocks","volume":"37","author":"Chia","year":"2005","journal-title":"Nat. Genet."},{"key":"10.1016\/j.neuropharm.2020.108297_bib13","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.tips.2014.11.004","article-title":"Current treatment strategies for inhibiting mTOR in cancer","volume":"36","author":"Chiarini","year":"2015","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.neuropharm.2020.108297_bib14","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.phrs.2016.03.039","article-title":"mTOR pathway inhibition as a new therapeutic strategy in epilepsy and epileptogenesis","volume":"107","author":"Citraro","year":"2016","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.neuropharm.2020.108297_bib15","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1007\/s12035-016-9827-0","article-title":"KU0063794, a dual mTORC1 and mTORC2 inhibitor, reduces neural tissue damage and locomotor impairment after spinal cord injury in mice","volume":"54","author":"Cordaro","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.neuropharm.2020.108297_bib16","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nrneurol.2016.81","article-title":"The mTOR signalling cascade: paving new roads to cure neurological disease","volume":"12","author":"Crino","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.neuropharm.2020.108297_bib17","doi-asserted-by":"crossref","first-page":"18024","DOI":"10.1038\/nrdp.2018.24","volume":"4","author":"Devinsky","year":"2018","journal-title":"Epilepsy. Nat. Rev. Dis. Primers."},{"key":"10.1016\/j.neuropharm.2020.108297_bib18","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1007\/s11064-017-2239-3","article-title":"A mesiotemporal lobe epilepsy mouse model","volume":"42","author":"Duveau","year":"2017","journal-title":"Neurochem. Res."},{"key":"10.1016\/j.neuropharm.2020.108297_bib19","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1111\/j.1528-1167.2007.01110.x","article-title":"The natural history and treatment of epilepsy in a murine model of tuberous sclerosis","volume":"48","author":"Erbayat-Altay","year":"2007","journal-title":"Epilepsia"},{"key":"10.1016\/j.neuropharm.2020.108297_bib20","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0158476","article-title":"Long-term use of everolimus in patients with tuberous sclerosis complex: final results from the EXIST-1 study","volume":"11","author":"Franz","year":"2016","journal-title":"PloS One"},{"key":"10.1016\/j.neuropharm.2020.108297_bib21","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1212\/CPJ.0000000000000514","article-title":"Everolimus for treatment-refractory seizures in TSC: extension of a randomized controlled trial","volume":"8","author":"Franz","year":"2018","journal-title":"Neurol. Clin. Pract."},{"key":"10.1016\/j.neuropharm.2020.108297_bib22","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1016\/S0140-6736(16)31419-2","article-title":"Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): a phase 3, randomised, double-blind, placebo-controlled study","volume":"388","author":"French","year":"2016","journal-title":"Lancet"},{"key":"10.1016\/j.neuropharm.2020.108297_bib23","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1111\/j.1528-1167.2012.03506.x","article-title":"Finding a better drug for epilepsy: the mTOR pathway as an antiepileptogenic target","volume":"53","author":"Galanopoulou","year":"2012","journal-title":"Epilepsia"},{"key":"10.1016\/j.neuropharm.2020.108297_bib24","doi-asserted-by":"crossref","first-page":"107817","DOI":"10.1016\/j.neuropharm.2019.107817","article-title":"Selective inhibition of mTORC1\/2 or PI3K\/mTORC1\/2 signaling does not prevent or modify epilepsy in the intrahippocampal kainate mouse model","volume":"162","author":"Gericke","year":"2020","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.neuropharm.2020.108297_bib25","doi-asserted-by":"crossref","first-page":"298","DOI":"10.3389\/fneur.2018.00298","article-title":"Signaling pathways and cellular mechanisms regulating mossy fiber sprouting in the development of epilepsy","volume":"9","author":"Godale","year":"2018","journal-title":"Front. Neurol."},{"key":"10.1016\/j.neuropharm.2020.108297_bib26","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.npep.2009.12.007","article-title":"Akt pathway activation and increased neuropeptide Y mRNA expression in the rat hippocampus: implications for seizure blockade","volume":"44","author":"Goto","year":"2010","journal-title":"Neuropeptides"},{"key":"10.1016\/j.neuropharm.2020.108297_bib27","doi-asserted-by":"crossref","first-page":"49","DOI":"10.2217\/fnl-2018-0001","article-title":"The mTOR pathway in treatment of epilepsy: a clinical update","volume":"13","author":"Griffith","year":"2018","journal-title":"Future Neurol."},{"key":"10.1016\/j.neuropharm.2020.108297_bib28","doi-asserted-by":"crossref","first-page":"8544","DOI":"10.18632\/oncotarget.2337","article-title":"Catalytic mTOR inhibitors can overcome intrinsic and acquired resistance to allosteric mTOR inhibitors","volume":"5","author":"Hassan","year":"2014","journal-title":"Oncotarget"},{"key":"10.1016\/j.neuropharm.2020.108297_bib29","series-title":"Models of Seizures and Epilepsy","first-page":"611","article-title":"Poststatus epilepticus models: focal kainic acid","author":"Henshall","year":"2017"},{"key":"10.1016\/j.neuropharm.2020.108297_bib30","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20225792","article-title":"PI3K\/mTOR pathway inhibition: opportunities in oncology and rare genetic diseases","volume":"20","author":"Hillmann","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.neuropharm.2020.108297_bib31","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.nbd.2010.05.024","article-title":"Pharmacological inhibition of the mammalian target of rapamycin pathway suppresses acquired epilepsy","volume":"40","author":"Huang","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.neuropharm.2020.108297_bib32","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/nrclinonc.2018.28","article-title":"Targeting the PI3K pathway in cancer: are we making headway?","volume":"15","author":"Janku","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.neuropharm.2020.108297_bib33","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1177\/1535759720905835","article-title":"mTORC2 steals the spotlight","volume":"20","author":"Jansen","year":"2020","journal-title":"Epilepsy Current"},{"key":"10.1016\/j.neuropharm.2020.108297_bib34","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1177\/0883073817696814","article-title":"Targeting the mammalian target of rapamycin for epileptic encephalopathies and malformations of cortical development","volume":"33","author":"Jeong","year":"2015","journal-title":"J. Child Neurol."},{"key":"10.1016\/j.neuropharm.2020.108297_bib35","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1111\/ajt.12669","article-title":"Everolimus inhibits anti-HLA I antibody-mediated endothelial cell signaling, migration and proliferation more potently than sirolimus","volume":"14","author":"Jin","year":"2014","journal-title":"Am. J. Transplant."},{"key":"10.1016\/j.neuropharm.2020.108297_bib36","series-title":"Modifying Genetic Epilepsies \u2013 Results from Studies on Tuberous Sclerosis Complex and Their Potential Mpact","author":"Jozwiak","year":"2020"},{"key":"10.1016\/j.neuropharm.2020.108297_bib37","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.1000412","article-title":"Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research","volume":"8","author":"Kilkenny","year":"2010","journal-title":"PLoS Biol."},{"key":"10.1016\/j.neuropharm.2020.108297_bib38","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1517\/14740338.2015.1040388","article-title":"Everolimus and sirolimus in transplantation - related but different","volume":"14","author":"Klawitter","year":"2015","journal-title":"Expet Opin. Drug Saf."},{"key":"10.1016\/j.neuropharm.2020.108297_bib39","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.cell.2012.03.017","article-title":"mTOR signaling in growth control and disease","volume":"149","author":"Laplante","year":"2012","journal-title":"Cell"},{"key":"10.1016\/j.neuropharm.2020.108297_bib40","first-page":"F1000Res","volume":"vol. 7","author":"Leach","year":"2018"},{"key":"10.1016\/j.neuropharm.2020.108297_bib41","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1080\/14737175.2019.1635457","article-title":"Everolimus as adjunctive therapy for tuberous sclerosis complex-associated partial-onset seizures","volume":"19","author":"Lechuga","year":"2019","journal-title":"Expert Rev. Neurother."},{"key":"10.1016\/j.neuropharm.2020.108297_bib42","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.neuron.2014.09.034","article-title":"The neurology of mTOR","volume":"84","author":"Lipton","year":"2014","journal-title":"Neuron"},{"key":"10.1016\/j.neuropharm.2020.108297_bib43","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1007\/s11064-012-0797-y","article-title":"Time-dependent modulation of mitogen activated protein kinases and AKT in rat hippocampus and cortex in the pilocarpine model of epilepsy","volume":"37","author":"Lopes","year":"2012","journal-title":"Neurochem. Res."},{"key":"10.1016\/j.neuropharm.2020.108297_bib44","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.yebeh.2017.05.040","article-title":"The relevance of inter- and intrastrain differences in mice and rats and their implications for models of seizures and epilepsy","volume":"73","author":"L\u00f6scher","year":"2017","journal-title":"Epilepsy Behav."},{"key":"10.1016\/j.neuropharm.2020.108297_bib45","doi-asserted-by":"crossref","first-page":"591","DOI":"10.3390\/ijms21020591","article-title":"Structural, molecular and functional alterations of the blood-brain barrier during epileptogenesis and epilepsy: a cause, consequence or both?","volume":"21","author":"L\u00f6scher","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.neuropharm.2020.108297_bib46","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1124\/pr.120.019539","article-title":"Drug resistance in epilepsy: clinical impact, potential mechanisms, and new innovative treatment options","volume":"72","author":"L\u00f6scher","year":"2020","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.neuropharm.2020.108297_bib47","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1007\/s13311-011-0039-z","article-title":"Interleukin-1beta biosynthesis inhibition reduces acute seizures and drug resistant chronic epileptic activity in mice","volume":"8","author":"Maroso","year":"2011","journal-title":"Neurotherapeutics"},{"key":"10.1016\/j.neuropharm.2020.108297_bib70","first-page":"5422","article-title":"Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: Effects on mTORC1 and Akt signaling lead to improved survival and function","volume":"28","author":"Meikle","year":"2008","journal-title":"Neurobiol.Dis."},{"key":"10.1016\/j.neuropharm.2020.108297_bib48","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s40263-014-0223-x","article-title":"mTOR inhibition in epilepsy: rationale and clinical perspectives","volume":"29","author":"Ostendorf","year":"2015","journal-title":"CNS Drugs"},{"key":"10.1016\/j.neuropharm.2020.108297_bib49","series-title":"The Mouse Brain in Stereotaxic Coordinates","author":"Paxinos","year":"2012"},{"key":"10.1016\/j.neuropharm.2020.108297_bib50","doi-asserted-by":"crossref","first-page":"10084","DOI":"10.1021\/acs.jmedchem.8b01262","article-title":"Discovery and preclinical characterization of 5-[4,6-Bis({3-oxa-8-azabicyclo[3.2.1]octan-8-yl})-1,3,5-triazin-2-yl]-4-(difluoro methyl)pyridin-2-amine (PQR620), a highly potent and selective mTORC1\/2 inhibitor for cancer and neurological disorders","volume":"61","author":"Rageot","year":"2018","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.neuropharm.2020.108297_bib51","doi-asserted-by":"crossref","first-page":"6241","DOI":"10.1021\/acs.jmedchem.9b00525","article-title":"(S)-4-(Difluoromethyl)-5-(4-(3-methylmorpholino)-6-morpholino-1,3,5-triazin-2-yl) pyridin-2-amine (PQR530), a potent, orally bioavailable, and brain-penetrable dual inhibitor of class I PI3K and mTOR kinase","volume":"62","author":"Rageot","year":"2019","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.neuropharm.2020.108297_bib52","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0306-4522(02)00064-7","article-title":"Evolution of hippocampal epileptic activity during the development of hippocampal sclerosis in a mouse model of temporal lobe epilepsy","volume":"112","author":"Riban","year":"2002","journal-title":"Neuroscience"},{"key":"10.1016\/j.neuropharm.2020.108297_bib53","doi-asserted-by":"crossref","first-page":"a022780","DOI":"10.1101\/cshperspect.a022780","article-title":"Mechanisms of action of antiseizure drugs and the ketogenic diet","volume":"6","author":"Rogawski","year":"2016","journal-title":"Cold Spring Harb. Perspect. Med"},{"key":"10.1016\/j.neuropharm.2020.108297_bib54","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","article-title":"mTOR signaling in growth, metabolism, and disease","volume":"168","author":"Saxton","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.neuropharm.2020.108297_bib55","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1111\/ejn.12835","article-title":"Activation of mTOR signaling pathway is secondary to neuronal excitability in a mouse model of mesio-temporal lobe epilepsy","volume":"41","author":"Shima","year":"2015","journal-title":"Eur. J. Neurosci."},{"key":"10.1016\/j.neuropharm.2020.108297_bib56","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/0306-4522(94)00463-F","article-title":"Morphogenetic effect of kainate on adult hippocampal neurons associated with a prolonged expression of brain-derived neurotrophic factor","volume":"64","author":"Suzuki","year":"1995","journal-title":"Neuroscience"},{"key":"10.1016\/j.neuropharm.2020.108297_bib57","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.neuroscience.2016.11.017","article-title":"Molecular neurobiology of mTOR","volume":"341","author":"Switon","year":"2017","journal-title":"Neuroscience"},{"key":"10.1016\/j.neuropharm.2020.108297_bib58","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/ana.25149","article-title":"Mechanistic target of rapamycin complex 1 and 2 in human temporal lobe epilepsy","volume":"83","author":"Talos","year":"2018","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.neuropharm.2020.108297_bib59","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.yebeh.2015.11.027","article-title":"Significant effects of sex, strain, and anesthesia in the intrahippocampal kainate mouse model of mesial temporal lobe epilepsy","volume":"55","author":"Twele","year":"2016","journal-title":"Epilepsy Behav."},{"key":"10.1016\/j.neuropharm.2020.108297_bib60","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/epi4.2","article-title":"The effects of carbamazepine in the intrahippocampal kainate model of temporal lobe epilepsy depend on seizure definition and mouse strain","volume":"1","author":"Twele","year":"2016","journal-title":"Epilepsia Open"},{"key":"10.1016\/j.neuropharm.2020.108297_bib61","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/epi4.12044","article-title":"The intrahippocampal kainate mouse model of mesial temporal lobe epilepsy: lack of electrographic seizure-like events in sham controls","volume":"2","author":"Twele","year":"2017","journal-title":"Epilepsia Open"},{"key":"10.1016\/j.neuropharm.2020.108297_bib62","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1002\/ana.10283","article-title":"Astrocyte-specific TSC1 conditional knockout mice exhibit abnormal neuronal organization and seizures","volume":"52","author":"Uhlmann","year":"2002","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.neuropharm.2020.108297_bib63","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.semcdb.2014.10.003","article-title":"Blood-brain barrier dysfunction, seizures and epilepsy","volume":"38","author":"van Vliet","year":"2015","journal-title":"Semin. Cell Dev. Biol."},{"key":"10.1016\/j.neuropharm.2020.108297_bib64","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1038\/nm.2982","article-title":"Before epilepsy unfolds: finding the epileptogenesis switch","volume":"18","author":"Vezzani","year":"2012","journal-title":"Nat. Med."},{"key":"10.1016\/j.neuropharm.2020.108297_bib65","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.ejca.2018.03.012","article-title":"First-in human, phase 1, dose-escalation pharmacokinetic and pharmacodynamic study of the oral dual PI3K and mTORC1\/2 inhibitor PQR309 in patients with advanced solid tumors (SAKK 67\/13)","volume":"96","author":"Wicki","year":"2018","journal-title":"Eur. J. Canc."},{"key":"10.1016\/j.neuropharm.2020.108297_bib66","doi-asserted-by":"crossref","first-page":"40","DOI":"10.4103\/2319-4170.110365","article-title":"Mammalian target of rapamycin (mTOR) pathways in neurological diseases","volume":"36","author":"Wong","year":"2013","journal-title":"Biomed. J."},{"key":"10.1016\/j.neuropharm.2020.108297_bib67","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.neuropharm.2015.05.008","article-title":"Rapamycin prevents cadmium-induced neuronal cell death via targeting both mTORC1 and mTORC2 pathways","volume":"97","author":"Xu","year":"2015","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.neuropharm.2020.108297_bib68","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s12974-017-0797-6","article-title":"Everolimus is better than rapamycin in attenuating neuroinflammation in kainic acid-induced seizures","volume":"14","author":"Yang","year":"2017","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.neuropharm.2020.108297_bib69","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1002\/ana.21331","article-title":"Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex","volume":"63","author":"Zeng","year":"2008","journal-title":"Ann. Neurol."}],"container-title":["Neuropharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0028390820303658?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0028390820303658?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T07:05:47Z","timestamp":1758438347000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0028390820303658"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12]]},"references-count":70,"alternative-id":["S0028390820303658"],"URL":"https:\/\/doi.org\/10.1016\/j.neuropharm.2020.108297","relation":{},"ISSN":["0028-3908"],"issn-type":[{"value":"0028-3908","type":"print"}],"subject":[],"published":{"date-parts":[[2020,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Novel brain permeant mTORC1\/2 inhibitors are as efficacious as rapamycin or everolimus in mouse models of acquired partial epilepsy and tuberous sclerosis complex","name":"articletitle","label":"Article Title"},{"value":"Neuropharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.neuropharm.2020.108297","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"108297"}}