Generic placeholder image

CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Review Article

An Insight into Molecular Mechanisms and Novel Therapeutic Approaches in Epileptogenesis

Author(s): Shareen Singh, Thakur Gurjeet Singh* and Ashish Kumar Rehni

Volume 19, Issue 10, 2020

Page: [750 - 779] Pages: 30

DOI: 10.2174/1871527319666200910153827

Price: $65

Abstract

Epilepsy is the second most common neurological disease with abnormal neural activity involving the activation of various intracellular signalling transduction mechanisms. The molecular and system biology mechanisms responsible for epileptogenesis are not well defined or understood. Neuroinflammation, neurodegeneration and Epigenetic modification elicit epileptogenesis. The excessive neuronal activities in the brain are associated with neurochemical changes underlying the deleterious consequences of excitotoxicity. The prolonged repetitive excessive neuronal activities extended to brain tissue injury by the activation of microglia regulating abnormal neuroglia remodelling and monocyte infiltration in response to brain lesions inducing axonal sprouting contributing to neurodegeneration. The alteration of various downstream transduction pathways resulted in intracellular stress responses associating endoplasmic reticulum, mitochondrial and lysosomal dysfunction, activation of nucleases, proteases mediated neuronal death. The recently novel pharmacological agents modulate various receptors like mTOR, COX-2, TRK, JAK-STAT, epigenetic modulators and neurosteroids are used for attenuation of epileptogenesis. Whereas the various molecular changes like the mutation of the cell surface, nuclear receptor and ion channels focusing on repetitive episodic seizures have been explored by preclinical and clinical studies. Despite effective pharmacotherapy for epilepsy, the inadequate understanding of precise mechanisms, drug resistance and therapeutic failure are the current fundamental problems in epilepsy. Therefore, the novel pharmacological approaches evaluated for efficacy on experimental models of epilepsy need to be identified and validated. In addition, we need to understand the downstream signalling pathways of new targets for the treatment of epilepsy. This review emphasizes on the current state of novel molecular targets as therapeutic approaches and future directions for the management of epileptogenesis. Novel pharmacological approaches and clinical exploration are essential to make new frontiers in curing epilepsy.

Keywords: Epilepsy, microglia, neurodegeneration, excitotoxicity, mitochondrial dysfunction, seizures.

Graphical Abstract

[1]
Tokudome K, Shimizu S, Serikawa T, Ohno Y. Function of synaptic vesicle protein 2A (SV2A) as a novel therapeutic target for epilepsy. Nihon yakurigaku zasshi Folia pharmacologica Japonica 2018; 152: 275-80.
[2]
Chipaux M, Vercueil L, Kaminska A, Mahon S, Charpier S. Persistence of cortical sensory processing during absence seizures in human and an animal model: evidence from EEG and intracellular recordings. PLoS One 2013; 8(3): e58180.
[http://dx.doi.org/10.1371/journal.pone.0058180] [PMID: 23483991]
[3]
Koutroumanidis M, Arzimanoglou A, Caraballo R, et al. The role of EEG in the diagnosis and classification of the epilepsy syndromes: a tool for clinical practice by the ILAE Neurophysiology Task Force (Part 2). Epileptic Disord 2017; 19(4): 385-437.
[http://dx.doi.org/10.1684/epd.2017.0952] [PMID: 29350182]
[4]
De Marchi LR, Corso JT, Zetehaku AC, Uchida CGP, Guaranha MSB, Yacubian EMT. Efficacy and safety of a video-EEG protocol for genetic generalized epilepsies. Epilepsy Behav 2017; 70(Pt A): 187-92.
[http://dx.doi.org/10.1016/j.yebeh.2017.03.029] [PMID: 28431366]
[5]
Hirose G. An overview of epilepsy: its history, classification, pathophysiology and management Brain and nerve 2013; 65: 509-20.
[6]
Marmura MJ, Kumpinsky AS. Refining the benefit/risk profile of anti-epileptic drugs in headache disorders. CNS Drugs 2018; 32(8): 735-46.
[http://dx.doi.org/10.1007/s40263-018-0555-z] [PMID: 30073584]
[7]
Dudek FE. Role of glial cells in seizures and epilepsy: intracellular calcium oscillations and spatial buffering. Epilepsy Curr 2002; 2(4): 137-9.
[http://dx.doi.org/10.1046/j.1535-7597.2002.t01-1-00052.x] [PMID: 15309145]
[8]
Moshé SL, Perucca E, Ryvlin P, Tomson T. Epilepsy: new advances. Lancet 2015; 385(9971): 884-98.
[http://dx.doi.org/10.1016/S0140-6736(14)60456-6] [PMID: 25260236]
[9]
Sander JW. The use of antiepileptic drugs--principles and practice. Epilepsia 2004; 45(Suppl. 6): 28-34.
[http://dx.doi.org/10.1111/j.0013-9580.2004.455005.x] [PMID: 15315513]
[10]
Villas N, Meskis MA, Goodliffe S. Dravet syndrome: Characteristics, comorbidities, and caregiver concerns. Epilepsy Behav 2017; 74: 81-6.
[http://dx.doi.org/10.1016/j.yebeh.2017.06.031] [PMID: 28732259]
[11]
Yoon Y, Jagoda A. New antiepileptic drugs and preparations. Emerg Med Clin North Am 2000; 18(4): 755-65.
[http://dx.doi.org/10.1016/S0733-8627(05)70157-7] [PMID: 11130937]
[12]
Chen R, Buyan A, Corry B. Voltage-gated sodium channel pharmacology: insights from molecular dynamics simulations. Adv Pharmacol 2017; 79: 255-85.
[http://dx.doi.org/10.1016/bs.apha.2017.02.002] [PMID: 28528671]
[13]
Johnston GA. GABA(A) receptor channel pharmacology. Curr Pharm Des 2005; 11(15): 1867-85.
[http://dx.doi.org/10.2174/1381612054021024] [PMID: 15974965]
[14]
Janmohamed M, Brodie MJ, Kwan P. Pharmacoresistance - Epidemiology, mechanisms, and impact on epilepsy treatment. Neuropharmacology 2020; 168: 107790.
[http://dx.doi.org/10.1016/j.neuropharm.2019.107790] [PMID: 31560910]
[15]
Guimarães J, Ribeiro JAM. Pharmacology of antiepileptic drugs in clinical practice. Neurologist 2010; 16(6): 353-7.
[http://dx.doi.org/10.1097/NRL.0b013e3181dba5d3] [PMID: 21150382]
[16]
Thiffault I, Speca DJ, Austin DC, et al. A novel epileptic encephalopathy mutation in KCNB1 disrupts Kv2.1 ion selectivity, expression, and localization. J Gen Physiol 2015; 146(5): 399-410.
[http://dx.doi.org/10.1085/jgp.201511444] [PMID: 26503721]
[17]
Sugiura Y, Ugawa Y. Epilepsy and ion channels Rinsho Shinkeigaku 2017; 57: 1-8.
[18]
Taing KD, O’Brien TJ, Williams DA, French CR. Anti-epileptic drug combination efficacy in an in vitro seizure model–phenytoin and valproate, lamotrigine and valproate. PLoS One 2017; 12(1): e0169974.
[http://dx.doi.org/10.1371/journal.pone.0169974] [PMID: 28076384]
[19]
Mula M. New antiepileptic drugs: molecular targets Cent Nerv Sys Agents in Med Chem 2009; 9: 79-86.
[http://dx.doi.org/10.2174/187152409788452063]
[20]
Zeng Z, Hill-Yardin EL, Williams D, O’Brien T, Serelis A, French CR. Effect of phenytoin on sodium conductances in rat hippocampal CA1 pyramidal neurons. J Neurophysiol 2016; 116(4): 1924-36.
[http://dx.doi.org/10.1152/jn.01060.2015] [PMID: 27489371]
[21]
Carcak N, Ozkara C. Seizures and antiepileptic drugs: from pathophysiology to clinical practice. Curr Pharm Des 2017; 23(42): 6376-88.
[http://dx.doi.org/10.2174/1381612823666171115101557] [PMID: 29141532]
[22]
Mathers DA, Wan X, Puil E. Barbiturate activation and modulation of GABA(A) receptors in neocortex. Neuropharmacology 2007; 52(4): 1160-8.
[http://dx.doi.org/10.1016/j.neuropharm.2006.12.004] [PMID: 17289092]
[23]
Chen CR, Tan R, Qu WM, et al. Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, exerts antiepileptic effects via the GABA/benzodiazepine receptor complex in mice. Br J Pharmacol 2011; 164(5): 1534-46.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01456.x] [PMID: 21518336]
[24]
Palma E, Ruffolo G, Cifelli P, Roseti C, Vliet EAV, Aronica E. Modulation of GABAA receptors in the treatment of epilepsy. Curr Pharm Des 2017; 23(37): 5563-8.
[http://dx.doi.org/10.2174/1381612823666170809100230] [PMID: 28799512]
[25]
Torolira D, Suchomelova L, Wasterlain CG, Niquet J. Phenobarbital and midazolam increase neonatal seizure-associated neuronal injury. Ann Neurol 2017; 82(1): 115-20.
[http://dx.doi.org/10.1002/ana.24967] [PMID: 28556259]
[26]
Morris G, Leite M, Kullmann DM, Pavlov I, Schorge S, Lignani G. Activity clamp provides insights into paradoxical effects of the anti-seizure drug carbamazepine. J Neurosci 2017; 37(22): 5484-95.
[http://dx.doi.org/10.1523/JNEUROSCI.3697-16.2017] [PMID: 28473648]
[27]
Gierbolini J, Giarratano M, Benbadis SR. Carbamazepine-related antiepileptic drugs for the treatment of epilepsy - a comparative review. Expert Opin Pharmacother 2016; 17(7): 885-8.
[http://dx.doi.org/10.1517/14656566.2016.1168399] [PMID: 26999402]
[28]
Sidach SS, Mintz IM. Kurtoxin, a gating modifier of neuronal high- and low-threshold Ca channels. J Neurosci 2002; 22(6): 2023-34.
[http://dx.doi.org/10.1523/JNEUROSCI.22-06-02023.2002] [PMID: 11896142]
[29]
Dezsi G, Ozturk E, Stanic D, et al. Ethosuximide reduces epileptogenesis and behavioral comorbidity in the GAERS model of genetic generalized epilepsy. Epilepsia 2013; 54(4): 635-43.
[http://dx.doi.org/10.1111/epi.12118] [PMID: 23464801]
[30]
Tringham E, Powell K L, Cain S M, et al. T-type calcium channel blockers that attenuate thalamic burst firing and suppress absence seizures Sci Transl Med 2012; 4: 121ra19-9.
[31]
Glauser TA, Holland K, O’Brien VP, et al. Childhood Absence Epilepsy Study Group. Pharmacogenetics of antiepileptic drug efficacy in childhood absence epilepsy. Ann Neurol 2017; 81(3): 444-53.
[http://dx.doi.org/10.1002/ana.24886] [PMID: 28165634]
[32]
Potschka H. Pharmacological treatment strategies: mechanisms of antiepileptic drugs. Epileptology 2013; 1: 31-7.
[http://dx.doi.org/10.1016/j.epilep.2012.11.004]
[33]
Brodie MJ. Antiepileptic drug therapy the story so far. Seizure 2010; 19(10): 650-5.
[http://dx.doi.org/10.1016/j.seizure.2010.10.027] [PMID: 21075011]
[34]
Michelucci R, Pasini E, Riguzzi P, Andermann E, Kälviäinen R, Genton P. Myoclonus and seizures in progressive myoclonus epilepsies: pharmacology and therapeutic trials. Epileptic Disord 2016; 18(S2): 145-53.
[http://dx.doi.org/10.1684/epd.2016.0861] [PMID: 27629998]
[35]
Brodie MJ. Pharmacological treatment of drug-resistant epilepsy in adults: a practical guide. Curr Neurol Neurosci Rep 2016; 16(9): 82.
[http://dx.doi.org/10.1007/s11910-016-0678-x] [PMID: 27443649]
[36]
LaGrotta C, Thomas A. Benzodiazepines and other sedatives, hypnotics, and anxiolytics. In: Marienfeld C. (eds) Absolute Addiction Psychiatry Review. Springer, Cham, 2020, pp. 139-51.
[http://dx.doi.org/10.1007/978-3-030-33404-8_9]
[37]
Shangguan Y, Liao H, Wang X. Clonazepam in the treatment of status epilepticus. Expert Rev Neurother 2015; 15(7): 733-40.
[http://dx.doi.org/10.1586/14737175.2015.1056781] [PMID: 26109227]
[38]
Simeone TA. Mechanisms of antiepileptic drug action Epilepsy: mechanisms, models, and translational perspectives. Boca Raton: CRC Press 2010; pp. 123-41.
[39]
Benbadis SR. Practical management issues for idiopathic generalized epilepsies. Epilepsia 2005; 46(Suppl. 9): 125-32.
[http://dx.doi.org/10.1111/j.1528-1167.2005.00324.x] [PMID: 16302886]
[40]
Sheybani L, Mercier N, Vulliémoz S. Pharmacology and epilepsy : update on the new antiepileptic drugs. Rev Med Suisse 2019; 15(648): 857-61.
[PMID: 31021570]
[41]
Potschka H. Role of CNS efflux drug transporters in antiepileptic drug delivery: overcoming CNS efflux drug transport. Adv Drug Deliv Rev 2012; 64(10): 943-52.
[http://dx.doi.org/10.1016/j.addr.2011.12.007] [PMID: 22210135]
[42]
Silvestro S, Mammana S, Cavalli E, Bramanti P, Mazzon E. Use of cannabidiol in the treatment of epilepsy: Efficacy and security in clinical trials. Molecules 2019; 24(8): 1459.
[http://dx.doi.org/10.3390/molecules24081459] [PMID: 31013866]
[43]
Yacubian EMT, de Araújo Filho GM. Management issues for patients with idiopathic generalized epilepsies. Epileptology 2013; 1: 1-10.
[http://dx.doi.org/10.1016/j.epilep.2012.11.001]
[44]
van Luijtelaar G, Sitnikova E. Global and focal aspects of absence epilepsy: The contribution of genetic models. Neurosci Biobehav Rev 2006; 30(7): 983-1003.
[http://dx.doi.org/10.1016/j.neubiorev.2006.03.002] [PMID: 16725200]
[45]
Porter RJ, Dhir A, Macdonald RL, Rogawski MA. Mechanisms of action of antiseizure drugs. Handb Clin Neurol 2012; 108: 663-81.
[http://dx.doi.org/10.1016/B978-0-444-52899-5.00021-6] [PMID: 22939059]
[46]
Luke M. Therapeutic drug monitoring of classical and newer anticonvulsants.Therapeutic drug monitoring: newer drugs and biomarkers. London: Elsevier Publishing 2012; 7: pp. 243-67.
[http://dx.doi.org/10.1016/B978-0-12-385467-4.00012-9]
[47]
Leclercq K, Matagne A, Provins L, Klitgaard H, Kaminski RM. Pharmacological profile of the novel antiepileptic drug candidate padsevonil: characterization in rodent seizure and epilepsy models. J Pharmacol Exp Ther 2020; 372(1): 11-20.
[http://dx.doi.org/10.1124/jpet.119.261222] [PMID: 31619464]
[48]
Soares-da-Silva P, Pires N, Bonifácio MJ, Loureiro AI, Palma N, Wright LC. Eslicarbazepine acetate for the treatment of focal epilepsy: an update on its proposed mechanisms of action. Pharmacol Res Perspect 2015; 3(2): e00124.
[http://dx.doi.org/10.1002/prp2.124] [PMID: 26038700]
[49]
Kitaura H, Shirozu H, Masuda H, Fukuda M, Fujii Y, Kakita A. Pathophysiological characteristics associated with epileptogenesis in human hippocampal sclerosis. EBioMedicine 2018; 29: 38-46.
[http://dx.doi.org/10.1016/j.ebiom.2018.02.013] [PMID: 29478873]
[50]
Bernhardt BC, Fadaie F, Liu M, et al. Temporal lobe epilepsy: Hippocampal pathology modulates connectome topology and controllability. Neurology 2019; 92(19): e2209-20.
[http://dx.doi.org/10.1212/WNL.0000000000007447] [PMID: 31004070]
[51]
Jarero-Basulto JJ, Gasca-Martínez Y, Rivera-Cervantes MC, Ureña-Guerrero ME, Feria-Velasco AI, Beas-Zarate C. Interactions between epilepsy and plasticity. Pharmaceuticals (Basel) 2018; 11(1): 17.
[http://dx.doi.org/10.3390/ph11010017] [PMID: 29414852]
[52]
Hamadi N, Sheikh A, Madjid N, et al. Increased pro-inflammatory cytokines, glial activation and oxidative stress in the hippocampus after short-term bilateral adrenalectomy. BMC Neurosci 2016; 17(1): 61.
[http://dx.doi.org/10.1186/s12868-016-0296-1] [PMID: 27586269]
[53]
Devinsky O, Vezzani A, O’Brien TJ, et al. Epilepsy. Nat Rev Dis Primers 2018; 4: 18024.
[http://dx.doi.org/10.1038/nrdp.2018.24] [PMID: 29722352]
[54]
Han H, Mann A, Ekstein D, Eyal S. Breaking bad: the structure and function of the blood-brain barrier in epilepsy. AAPS J 2017; 19(4): 973-88.
[http://dx.doi.org/10.1208/s12248-017-0096-2] [PMID: 28550637]
[55]
Dadas A, Janigro D. Breakdown of blood brain barrier as a mechanism of post-traumatic epilepsy. Neurobiol Dis 2019; 123: 20-6.
[http://dx.doi.org/10.1016/j.nbd.2018.06.022] [PMID: 30030025]
[56]
Tang F, Hartz AMS, Bauer B. Drug-resistant epilepsy: multiple hypotheses, few answers. Front Neurol 2017; 8: 301.
[http://dx.doi.org/10.3389/fneur.2017.00301] [PMID: 28729850]
[57]
Bjørke AB, Nome CG, Falk RS, Gjerstad L, Taubøll E, Heuser K. Evaluation of long-term antiepileptic drug use in patients with temporal lobe epilepsy: Assessment of risk factors for drug resistance and polypharmacy. Seizure 2018; 61: 63-70.
[http://dx.doi.org/10.1016/j.seizure.2018.07.011] [PMID: 30099235]
[58]
Deng X, Xie Y, Chen Y. Effect of neuroinflammation on ABC transporters: possible contribution to refractory epilepsy. CNS Neurol Disord Drug Targets 2018; 17(10): 728-35.
[http://dx.doi.org/10.2174/1871527317666180828121820] [PMID: 30152292]
[59]
Shen XM, Cheng J. Effects of MDR1 (C3435T) polymorphism on resistance, uptake, and efflux to antiepileptic drugs. DNA Cell Biol 2019; 38(3): 250-5.
[http://dx.doi.org/10.1089/dna.2018.4553] [PMID: 30632789]
[60]
Uchida Y, Ohtsuki S, Terasaki T. Pharmacoproteomics-based reconstruction of in vivo P-glycoprotein function at blood-brain barrier and brain distribution of substrate verapamil in pentylenetetrazole-kindled epilepsy, spontaneous epilepsy, and phenytoin treatment models. Drug Metab Dispos 2014; 42(10): 1719-26.
[http://dx.doi.org/10.1124/dmd.114.059055] [PMID: 25061162]
[61]
Xie Y, Shao Y, Deng X, Wang M, Chen Y. MicroRNA-298 reverses multidrug resistance to antiepileptic drugs by suppressing MDR1/P-gp expression in vitro. Front Neurosci 2018; 12: 602.
[http://dx.doi.org/10.3389/fnins.2018.00602] [PMID: 30210283]
[62]
Zamay T N, Zamay G S, Shnayder N A, et al. Nucleic acid aptamers for molecular therapy of epilepsy and blood–brain barrier damages Mole Ther Nucleic Acids 19: 157-67.
[http://dx.doi.org/10.1016/j.omtn.2019.10.042]
[63]
Leandro K, Bicker J, Alves G, Falcão A, Fortuna A. ABC transporters in drug-resistant epilepsy: mechanisms of upregulation and therapeutic approaches. Pharmacol Res 2019; 144: 357-76.
[http://dx.doi.org/10.1016/j.phrs.2019.04.031] [PMID: 31051235]
[64]
Zibell G, Unkrüer B, Pekcec A, et al. Prevention of seizure-induced up-regulation of endothelial P-glycoprotein by COX-2 inhibition. Neuropharmacology 2009; 56(5): 849-55.
[http://dx.doi.org/10.1016/j.neuropharm.2009.01.009] [PMID: 19371577]
[65]
Gagliardo T, Gandini G, Gallucci A, et al. ABCB1 c.-6-180T>G polymorphism and clinical risk factors in a multi-breed cohort of dogs with refractory idiopathic epilepsy. Vet J 2019; 253: 105378.
[http://dx.doi.org/10.1016/j.tvjl.2019.105378] [PMID: 31685133]
[66]
Bauer B, Hartz AM, Lucking JR, Yang X, Pollack GM, Miller DS. Coordinated nuclear receptor regulation of the efflux transporter, Mrp2, and the phase-II metabolizing enzyme, GSTpi, at the blood-brain barrier. J Cereb Blood Flow Metab 2008; 28(6): 1222-34.
[http://dx.doi.org/10.1038/jcbfm.2008.16] [PMID: 18349876]
[67]
Yu N, Zhang YF, Zhang K, Cheng YF, Ma HY, Di Q. Pregnane X receptor not nuclear factor-kappa B up-regulates P-glycoprotein expression in the brain of chronic epileptic rats induced by kainic acid. Neurochem Res 2017; 42(8): 2167-77.
[http://dx.doi.org/10.1007/s11064-017-2224-x] [PMID: 28303499]
[68]
Rehni AK, Singh TG. Modulation of leukotriene D4 attenuates the development of seizures in mice. Prostaglandins Leukot Essent Fatty Acids 2011; 85(2): 97-106.
[http://dx.doi.org/10.1016/j.plefa.2011.04.003] [PMID: 21641195]
[69]
Chouchi M, Klaa H, Ben-Youssef Turki I, Hila L. ABCB1 Polymorphisms and Drug-Resistant Epilepsy in a Tunisian Population. Dis Markers 2019; 2019: 1343650.
[http://dx.doi.org/10.1155/2019/1343650] [PMID: 31871496]
[70]
Fricke-Galindo I, Jung-Cook H, LLerena A, López-López M. Pharmacogenetics of adverse reactions to antiepileptic drugs. Neurologia 2018; 33(3): 165-76.
[http://dx.doi.org/10.1016/j.nrl.2015.03.005] [PMID: 25976948]
[71]
Lopez-Garcia MA, Feria-Romero IA, Fernando-Serrano H, Escalante-Santiago D, Grijalva I, Orozco-Suarez S. Genetic polymorphisms associated with antiepileptic metabolism. Front Biosci (Elite Ed) 2014; 6: 377-86.
[http://dx.doi.org/10.2741/713] [PMID: 24896213]
[72]
Møller HS, Rodin E, Aukland P, Lando M, Christiansen EB, Beier CP. Epidemiology-based mortality score is associated with long-term mortality after status epilepticus. Neurocrit Care 2019; 31(1): 135-41.
[http://dx.doi.org/10.1007/s12028-018-0663-0] [PMID: 30607827]
[73]
Claassen J, Goldstein JN. Emergency neurological life support: status epilepticus. Neurocrit Care 2017; 27(Suppl. 1): 152-8.
[http://dx.doi.org/10.1007/s12028-017-0460-1] [PMID: 28913605]
[74]
Wang J, Li Y, Huang WH, et al. The protective effect of aucubin from eucommia ulmoides against status epilepticus by inducing autophagy and inhibiting necroptosis. Am J Chin Med 2017; 45(3): 557-73.
[http://dx.doi.org/10.1142/S0192415X17500331] [PMID: 28387136]
[75]
Dutra MRH, Feliciano RDS, Jacinto KR, et al. Protective role of UCP2 in oxidative stress and apoptosis during the silent phase of an experimental model of epilepsy induced by pilocarpine. Oxid Med Cell Longev 2018; 2018: 6736721.
[http://dx.doi.org/10.1155/2018/6736721] [PMID: 30159115]
[76]
Nelson SE, Varelas PN. Status epilepticus, refractory status epilepticus, and super-refractory status epilepticus. Continuum (Minneap Minn) 2018; 24(6): 1683-707.
[http://dx.doi.org/10.1212/CON.0000000000000668] [PMID: 30516601]
[77]
Li Q, Han Y, Du J, et al. Alterations of apoptosis and autophagy in developing brain of rats with epilepsy: Changes in LC3, P62, Beclin-1 and Bcl-2 levels. Neurosci Res 2018; 130: 47-55.
[http://dx.doi.org/10.1016/j.neures.2017.08.004] [PMID: 28807642]
[78]
Wang Z, Zhou L, An D, et al. TRPV4-induced inflammatory response is involved in neuronal death in pilocarpine model of temporal lobe epilepsy in mice. Cell Death Dis 2019; 10: 1-10.
[79]
Singh N, Saha L, Kumari P, et al. Effect of dimethyl fumarate on neuroinflammation and apoptosis in pentylenetetrazol kindling model in rats. Brain Res Bull 2019; 144: 233-45.
[http://dx.doi.org/10.1016/j.brainresbull.2018.11.013] [PMID: 30472152]
[80]
Sibarov DA, Antonov SM. Calcium-dependent desensitization of NMDA receptors. Biochemistry (Mosc) 2018; 83(10): 1173-83.
[http://dx.doi.org/10.1134/S0006297918100036] [PMID: 30472955]
[81]
Zhou Z, Austin GL, Young LEA, Johnson LA, Sun R. Mitochondrial metabolism in major neurological diseases. Cells 2018; 7(12): 229.
[http://dx.doi.org/10.3390/cells7120229] [PMID: 30477120]
[82]
Wang BH, Hou Q, Lu YQ, et al. Ketogenic diet attenuates neuronal injury via autophagy and mitochondrial pathways in pentylenetetrazol-kindled seizures. Brain Res 2018; 1678: 106-15.
[http://dx.doi.org/10.1016/j.brainres.2017.10.009] [PMID: 29056525]
[83]
Dingledine R, Varvel NH, Dudek FE. When and how do seizures kill neurons, and is cell death relevant to epileptogenesis? Adv Exp Med Biol 2014; 813(813): 109-22.
[http://dx.doi.org/10.1007/978-94-017-8914-1_9] [PMID: 25012371]
[84]
Glick D, Barth S, Macleod KF. Autophagy: cellular and molecular mechanisms. J Pathol 2010; 221(1): 3-12.
[http://dx.doi.org/10.1002/path.2697] [PMID: 20225336]
[85]
Cai Q, Gan J, Luo R, et al. The role of necroptosis in status epilepticus-induced brain injury in juvenile rats. Epilepsy Behav 2017; 75: 134-42.
[http://dx.doi.org/10.1016/j.yebeh.2017.05.025] [PMID: 28863321]
[86]
Marshall KD, Baines CP. Necroptosis: is there a role for mitochondria? Front Physiol 2014; 5: 323.
[http://dx.doi.org/10.3389/fphys.2014.00323] [PMID: 25206339]
[87]
Olive MF, Powell G, McClure E, Gipson CD. Neurotransmitter Systems: Glutamate In: The Therapeutic Use of N-Acetylcysteine (NAC) in Medicine. 2019; pp. 19-28.
[88]
Hotka M, Kubista H. The paroxysmal depolarization shift in epilepsy research. Int J Biochem Cell Biol 2019; 107: 77-81.
[http://dx.doi.org/10.1016/j.biocel.2018.12.006] [PMID: 30557621]
[89]
González OC, Krishnan GP, Timofeev I, Bazhenov M. Ionic and synaptic mechanisms of seizure generation and epileptogenesis. Neurobiol Dis 2019; 130: 104485.
[http://dx.doi.org/10.1016/j.nbd.2019.104485] [PMID: 31150792]
[90]
Staley K. Molecular mechanisms of epilepsy. Nat Neurosci 2015; 18(3): 367-72.
[http://dx.doi.org/10.1038/nn.3947] [PMID: 25710839]
[91]
Sakkaki S, Gangarossa G, Lerat B, et al. Blockade of T-type calcium channels prevents tonic-clonic seizures in a maximal electroshock seizure model. Neuropharmacology 2016; 101: 320-9.
[http://dx.doi.org/10.1016/j.neuropharm.2015.09.032] [PMID: 26456350]
[92]
Cain SM, Garcia E, Waheed Z, Jones KL, Bushell TJ, Snutch TP. GABAB receptors suppress burst-firing in reticular thalamic neurons. Channels (Austin) 2017; 11(6): 574-86.
[http://dx.doi.org/10.1080/19336950.2017.1358836] [PMID: 28742985]
[93]
Werner FM, Coveñas R. Neural networks in generalized epilepsy and novel antiepileptic drugs. Curr Pharm Des 2019; 25(4): 396-400.
[http://dx.doi.org/10.2174/1381612825666190319121505] [PMID: 30892153]
[94]
Peterlik D, Flor PJ, Uschold-Schmidt N. The emerging role of metabotropic glutamate receptors in the pathophysiology of chronic stress-related disorders. Curr Neuropharmacol 2016; 14(5): 514-39.
[http://dx.doi.org/10.2174/1570159X13666150515234920] [PMID: 27296643]
[95]
Sfaello I, Baud O, Arzimanoglou A, Gressens P. Topiramate prevents excitotoxic damage in the newborn rodent brain. Neurobiol Dis 2005; 20(3): 837-48.
[http://dx.doi.org/10.1016/j.nbd.2005.05.019] [PMID: 16009561]
[96]
Fukushima K, Tabata Y, Imaizumi Y, et al. Characterization of human hippocampal neural stem/progenitor cells and their application to physiologically relevant assays for multiple ionotropic glutamate receptors. J Biomol Screen 2014; 19(8): 1174-84.
[http://dx.doi.org/10.1177/1087057114541149] [PMID: 24980597]
[97]
Köhling R, Wolfart J. Potassium channels in epilepsy. Cold Spring Harb Perspect Med 2016; 6(5): a022871.
[http://dx.doi.org/10.1101/cshperspect.a022871] [PMID: 27141079]
[98]
Ishii A, Fukuma G, Uehara A, et al. A de novo KCNQ2 mutation detected in non-familial benign neonatal convulsions. Brain Dev 2009; 31(1): 27-33.
[http://dx.doi.org/10.1016/j.braindev.2008.05.010] [PMID: 18640800]
[99]
Barrese V, Miceli F, Soldovieri MV, et al. Neuronal potassium channel openers in the management of epilepsy: role and potential of retigabine. Clin Pharmacol 2010; 2: 225-36.
[PMID: 22291509]
[100]
Manville RW, Abbott GW. Cilantro leaf harbors a potent potassium channel-activating anticonvulsant. FASEB J 2019; 33(10): 11349-63.
[http://dx.doi.org/10.1096/fj.201900485R] [PMID: 31311306]
[101]
Pantazis A, Kaneko M, Westerlund AM, Delemotte L, Saitta S, Olcese R. A De Novo Mutation Associated with Epilepsy Enhances KV1. 2 Voltage Dependence, Suppressing Neuronal Excitability. Biophys J 2019; 116: 247a.
[http://dx.doi.org/10.1016/j.bpj.2018.11.1351]
[102]
Liss B, Roeper J. Molecular physiology of neuronal K-ATP channels (review). Mol Membr Biol 2001; 18(2): 117-27.
[http://dx.doi.org/10.1080/09687680110047373] [PMID: 11463204]
[103]
Soundarapandian MM, Wu D, Zhong X, et al. Expression of functional Kir6.1 channels regulates glutamate release at CA3 synapses in generation of epileptic form of seizures. J Neurochem 2007; 103(5): 1982-8.
[http://dx.doi.org/10.1111/j.1471-4159.2007.04883.x] [PMID: 17883401]
[104]
Huang CW, Huang CC, Cheng JT, Tsai JJ, Wu SN. Glucose and hippocampal neuronal excitability: role of ATP-sensitive potassium channels. J Neurosci Res 2007; 85(7): 1468-77.
[http://dx.doi.org/10.1002/jnr.21284] [PMID: 17410601]
[105]
Mohammadi F, Shakiba S, Mehrzadi S, Afshari K, Rahimnia AH, Dehpour AR. Anticonvulsant effect of melatonin through ATP-sensitive channels in mice. Fundam Clin Pharmacol 2020; 34(1): 148-55.
[http://dx.doi.org/10.1111/fcp.12490] [PMID: 31197879]
[106]
Hund TJ, Mohler PJ. Differential roles for SUR subunits in KATP channel membrane targeting and regulation. Am J Physiol Heart Circ Physiol 2011; 300(1): H33-5.
[http://dx.doi.org/10.1152/ajpheart.01088.2010] [PMID: 21057044]
[107]
Reichold M, Zdebik AA, Lieberer E, et al. KCNJ10 gene mutations causing EAST syndrome (epilepsy, ataxia, sensorineural deafness, and tubulopathy) disrupt channel function. Proc Natl Acad Sci USA 2010; 107(32): 14490-5.
[http://dx.doi.org/10.1073/pnas.1003072107] [PMID: 20651251]
[108]
Wickenden AD. Potassium channels as anti-epileptic drug targets. Neuropharmacology 2002; 43(7): 1055-60.
[http://dx.doi.org/10.1016/S0028-3908(02)00237-X] [PMID: 12504910]
[109]
Yamada K, Ji JJ, Yuan H, et al. Protective role of ATP-sensitive potassium channels in hypoxia-induced generalized seizure. Science 2001; 292(5521): 1543-6.
[http://dx.doi.org/10.1126/science.1059829] [PMID: 11375491]
[110]
Boison D, Steinhäuser C. Epilepsy and astrocyte energy metabolism. Glia 2018; 66(6): 1235-43.
[http://dx.doi.org/10.1002/glia.23247] [PMID: 29044647]
[111]
Higashi H, Kinjo T, Uno K, Kuramoto N. Regulatory effects associated with changes in intracellular potassium level in susceptibility to mitochondrial depolarization and excitotoxicity. Neurochem Int 2020; 133: 104627.
[http://dx.doi.org/10.1016/j.neuint.2019.104627] [PMID: 31805298]
[112]
Sheikhi M, Shirzadian A, Dehdashtian A, et al. Involvement of ATP-sensitive potassium channels and the opioid system in the anticonvulsive effect of zolpidem in mice. Epilepsy Behav 2016; 62: 291-6.
[http://dx.doi.org/10.1016/j.yebeh.2016.07.014] [PMID: 27521722]
[113]
Egberongbe YI, Gentleman SM, Falkai P, Bogerts B, Polak JM, Roberts GW. The distribution of nitric oxide synthase immunoreactivity in the human brain. Neuroscience 1994; 59(3): 561-78.
[http://dx.doi.org/10.1016/0306-4522(94)90177-5] [PMID: 7516503]
[114]
Murphy S. Production of nitric oxide by glial cells: regulation and potential roles in the CNS. Glia 2000; 29(1): 1-13.
[http://dx.doi.org/10.1002/(SICI)1098-1136(20000101)29:1<1::AID-GLIA1>3.0.CO;2-N] [PMID: 10594918]
[115]
Picón-Pagès P, Garcia-Buendia J, Muñoz FJ. Functions and dysfunctions of nitric oxide in brain. Biochim Biophys Acta Mol Basis Dis 2019; 1865(8): 1949-67.
[http://dx.doi.org/10.1016/j.bbadis.2018.11.007] [PMID: 30500433]
[116]
Cui J, Wang G, Kandhare AD, Mukherjee-Kandhare AA, Bodhankar SL. Neuroprotective effect of naringin, a flavone glycoside in quinolinic acid-induced neurotoxicity: Possible role of PPAR-γ, Bax/Bcl-2, and caspase-3. Food Chem Toxicol 2018; 121: 95-108.
[http://dx.doi.org/10.1016/j.fct.2018.08.028] [PMID: 30130594]
[117]
Yu T, Yu H, Zhang B, et al. Promising neuroprotective function for m2 microglia in kainic acid-induced neurotoxicity via the down-regulation of NF-κB and caspase 3 signaling pathways. Neuroscience 2019; 406: 86-96.
[http://dx.doi.org/10.1016/j.neuroscience.2019.03.002] [PMID: 30858108]
[118]
Paillard T, Rolland Y, de Souto Barreto P. Protective effects of physical exercise in Alzheimer’s disease and Parkinson’s disease: a narrative review. J Clin Neurol 2015; 11(3): 212-9.
[http://dx.doi.org/10.3988/jcn.2015.11.3.212] [PMID: 26174783]
[119]
Yasuda H, Fujii M, Fujisawa H, Ito H, Suzuki M. Changes in nitric oxide synthesis and epileptic activity in the contralateral hippocampus of rats following intrahippocampal kainate injection. Epilepsia 2001; 42(1): 13-20.
[http://dx.doi.org/10.1046/j.1528-1157.2001.083032.x] [PMID: 11207780]
[120]
Gupta RC, Dettbarn WD. Prevention of kainic acid seizures-induced changes in levels of nitric oxide and high-energy phosphates by 7-nitroindazole in rat brain regions. Brain Res 2003; 981(1-2): 184-92.
[http://dx.doi.org/10.1016/S0006-8993(03)03034-8] [PMID: 12885440]
[121]
Méndez-Armenta M, Nava-Ruíz C, Juárez-Rebollar D, Rodríguez-Martínez E, Yescas Gómez P. Oxidative stress associated with neuronal apoptosis in experimental models of epilepsy Oxi Med Cellular longev 2014.
[http://dx.doi.org/10.1155/2014/293689]
[122]
Wojtal K, Gniatkowska-Nowakowska A, Czuczwar SJ. Is nitric oxide involved in the anticonvulsant action of antiepileptic drugs? Pol J Pharmacol 2003; 55(4): 535-42.
[PMID: 14581711]
[123]
Rehni AK, Singh TG, Kalra R, Singh N. Pharmacological inhibition of inducible nitric oxide synthase attenuates the development of seizures in mice. Nitric Oxide 2009; 21(2): 120-5.
[http://dx.doi.org/10.1016/j.niox.2009.06.001] [PMID: 19559095]
[124]
Banach M, Piskorska B, Czuczwar SJ, Borowicz KK. Nitric oxide, epileptic seizures, and action of antiepileptic drugs. CNS Neurol Disord Drug Targets 2011; 10(7): 808-19.
[http://dx.doi.org/10.2174/187152711798072347] [PMID: 21999730]
[125]
Mohseni G, Ostadhadi S, Akbarian R, Chamanara M, Norouzi-Javidan A, Dehpour AR. Anticonvulsant effect of dextrometrophan on pentylenetetrazole-induced seizures in mice: Involvement of nitric oxide and N-methyl-d-aspartate receptors. Epilepsy Behav 2016; 65: 49-55.
[http://dx.doi.org/10.1016/j.yebeh.2016.08.001] [PMID: 27875784]
[126]
De Sarro G, Gareri P, Falconi U, De Sarro A. 7-Nitroindazole potentiates the antiseizure activity of some anticonvulsants in DBA/2 mice. Eur J Pharmacol 2000; 394(2-3): 275-88.
[http://dx.doi.org/10.1016/S0014-2999(00)00086-8] [PMID: 10771293]
[127]
Calabrese F, Rossetti AC, Racagni G, Gass P, Riva MA, Molteni R. Brain-derived neurotrophic factor: a bridge between inflammation and neuroplasticity. Front Cell Neurosci 2014; 8: 430.
[http://dx.doi.org/10.3389/fncel.2014.00430] [PMID: 25565964]
[128]
Sasaki N, Sato T, Ohler A, O’Rourke B, Marbán E. Activation of mitochondrial ATP-dependent potassium channels by nitric oxide. Circulation 2000; 101(4): 439-45.
[http://dx.doi.org/10.1161/01.CIR.101.4.439] [PMID: 10653837]
[129]
Sun HS, Feng ZP. Neuroprotective role of ATP-sensitive potassium channels in cerebral ischemia. Acta Pharmacol Sin 2013; 34(1): 24-32.
[http://dx.doi.org/10.1038/aps.2012.138] [PMID: 23123646]
[130]
Robson SC, Sévigny J, Zimmermann H. The E-NTPDase family of ectonucleotidases: Structure function relationships and pathophysiological significance. Purinergic Signal 2006; 2(2): 409-30.
[http://dx.doi.org/10.1007/s11302-006-9003-5] [PMID: 18404480]
[131]
Huang L, Otrokocsi L, Sperlágh B. Role of P2 receptors in normal brain development and in neurodevelopmental psychiatric disorders. Brain Res Bull 2019; 151: 55-64.
[http://dx.doi.org/10.1016/j.brainresbull.2019.01.030] [PMID: 30721770]
[132]
Engel T, Jimenez-Pacheco A, Miras-Portugal MT, Diaz-Hernandez M, Henshall DC. P2X7 receptor in epilepsy; role in pathophysiology and potential targeting for seizure control. Int J Physiol Pathophysiol Pharmacol 2012; 4(4): 174-87.
[PMID: 23320131]
[133]
Song P, Hu J, Liu X, Deng X. Increased expression of the P2X7 receptor in temporal lobe epilepsy: Animal models and clinical evidence. Mol Med Rep 2019; 19(6): 5433-9.
[http://dx.doi.org/10.3892/mmr.2019.10202] [PMID: 31059094]
[134]
Fischer W, Franke H, Krügel U, et al. Critical evaluation of P2X7 receptor antagonists in selected seizure models. PLoS One 2016; 11(6): e0156468.
[http://dx.doi.org/10.1371/journal.pone.0156468] [PMID: 27281030]
[135]
Khan MT, Liu J, Nerlich J, Tang Y, Franke H, Illes P. Regulation of P2X7 receptor function of neural progenitor cells in the hippocampal subgranular zone by neuronal activity in the dentate gyrus. Neuropharmacology 2018; 140: 139-49.
[http://dx.doi.org/10.1016/j.neuropharm.2018.08.001] [PMID: 30092245]
[136]
Del Puerto A, Wandosell F, Garrido JJ. Neuronal and glial purinergic receptors functions in neuron development and brain disease. Front Cell Neurosci 2013; 7: 197.
[http://dx.doi.org/10.3389/fncel.2013.00197] [PMID: 24191147]
[137]
Jimenez-Pacheco A, Diaz-Hernandez M, Arribas-Blázquez M, et al. Transient P2X7 receptor antagonism produces lasting reductions in spontaneous seizures and gliosis in experimental temporal lobe epilepsy. J Neurosci 2016; 36(22): 5920-32.
[http://dx.doi.org/10.1523/JNEUROSCI.4009-15.2016] [PMID: 27251615]
[138]
Carlson SL, Kumar S, Werner DF, Comerford CE, Morrow AL. Ethanol activation of protein kinase A regulates GABAA α1 receptor function and trafficking in cultured cerebral cortical neurons. J Pharmacol Exp Ther 2013; 345(2): 317-25.
[http://dx.doi.org/10.1124/jpet.112.201954] [PMID: 23408117]
[139]
Mueller M, Schoeberlein A, Zhou J, et al. PreImplantation Factor bolsters neuroprotection via modulating Protein Kinase A and Protein Kinase C signaling. Cell Death Differ 2015; 22(12): 2078-86.
[http://dx.doi.org/10.1038/cdd.2015.55] [PMID: 25976303]
[140]
Tiwari MN, Mohan S, Biala Y, Yaari Y. Protein kinase A-mediated suppression of the slow afterhyperpolarizing KCa3. 1 current in temporal lobe epilepsy. J Neurosci 2019; 39(50): 9914-26.
[http://dx.doi.org/10.1523/JNEUROSCI.1603-19.2019] [PMID: 31672789]
[141]
Bracey JM, Kurz JE, Low B, Churn SB. Prolonged seizure activity leads to increased Protein Kinase A activation in the rat pilocarpine model of status epilepticus. Brain Res 2009; 1283: 167-76.
[http://dx.doi.org/10.1016/j.brainres.2009.05.066] [PMID: 19501060]
[142]
Merlin LR. Impact of protein kinase C activation on status epilepticus and epileptogenesis: oh, what a tangled web. Epilepsy Curr 2008; 8(4): 101-3.
[http://dx.doi.org/10.1111/j.1535-7511.2008.00256.x] [PMID: 18596877]
[143]
Zhu F, Kai J, Chen L, et al. Akt inhibitor perifosine prevents epileptogenesis in a rat model of temporal lobe epilepsy. Neurosci Bull 2018; 34(2): 283-90.
[http://dx.doi.org/10.1007/s12264-017-0165-7] [PMID: 28786074]
[144]
Takei N, Nawa H. mTOR signaling and its roles in normal and abnormal brain development. Front Mol Neurosci 2014; 7: 28.
[http://dx.doi.org/10.3389/fnmol.2014.00028] [PMID: 24795562]
[145]
Kesidou E, Lagoudaki R, Touloumi O, Poulatsidou KN, Simeonidou C. Autophagy and neurodegenerative disorders. Neural Regen Res 2013; 8(24): 2275-83.
[PMID: 25206537]
[146]
Maiese K. Targeting molecules to medicine with mTOR, autophagy and neurodegenerative disorders. Br J Clin Pharmacol 2016; 82(5): 1245-66.
[http://dx.doi.org/10.1111/bcp.12804] [PMID: 26469771]
[147]
Wong M. Mammalian target of rapamycin (mTOR) inhibition as a potential antiepileptogenic therapy: From tuberous sclerosis to common acquired epilepsies. Epilepsia 2010; 51(1): 27-36.
[http://dx.doi.org/10.1111/j.1528-1167.2009.02341.x] [PMID: 19817806]
[148]
Meng XF, Yu JT, Song JH, Chi S, Tan L. Role of the mTOR signaling pathway in epilepsy. J Neurol Sci 2013; 332(1-2): 4-15.
[http://dx.doi.org/10.1016/j.jns.2013.05.029] [PMID: 23773767]
[149]
Sadowski K, Kotulska-Jóźwiak K, Jóźwiak S. Role of mTOR inhibitors in epilepsy treatment. Pharmacol Rep 2015; 67(3): 636-46.
[http://dx.doi.org/10.1016/j.pharep.2014.12.017] [PMID: 25933981]
[150]
Holmes GL, Stafstrom CE. Tuberous Sclerosis Study Group. Tuberous sclerosis complex and epilepsy: recent developments and future challenges. Epilepsia 2007; 48(4): 617-30.
[http://dx.doi.org/10.1111/j.1528-1167.2007.01035.x] [PMID: 17386056]
[151]
Orlova KA, Crino PB. The tuberous sclerosis complex. Ann N Y Acad Sci 2010; 1184: 87-105.
[http://dx.doi.org/10.1111/j.1749-6632.2009.05117.x] [PMID: 20146692]
[152]
Crino PB. mTOR signaling in epilepsy: insights from malformations of cortical development. Cold Spring Harb Perspect Med 2015; 5(4): a022442.
[http://dx.doi.org/10.1101/cshperspect.a022442] [PMID: 25833943]
[153]
Napolioni V, Moavero R, Curatolo P. Recent advances in neurobiology of tuberous sclerosis complex. Brain Dev 2009; 31(2): 104-13.
[http://dx.doi.org/10.1016/j.braindev.2008.09.013] [PMID: 19028034]
[154]
Heras-Sandoval D, Pérez-Rojas JM, Hernández-Damián J, Pedraza-Chaverri J. The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration. Cell Signal 2014; 26(12): 2694-701.
[http://dx.doi.org/10.1016/j.cellsig.2014.08.019] [PMID: 25173700]
[155]
Abuhagr AM, Maclea KS, Chang ES, Mykles DL. Mechanistic target of rapamycin (mTOR) signaling genes in decapod crustaceans: cloning and tissue expression of mTOR, Akt, Rheb, and p70 S6 kinase in the green crab, Carcinus maenas, and blackback land crab, Gecarcinus lateralis. Comp Biochem Physiol A Mol Integr Physiol 2014; 168: 25-39.
[http://dx.doi.org/10.1016/j.cbpa.2013.11.008] [PMID: 24269559]
[156]
Yap TA, Garrett MD, Walton MI, Raynaud F, de Bono JS, Workman P. Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises. Curr Opin Pharmacol 2008; 8(4): 393-412.
[http://dx.doi.org/10.1016/j.coph.2008.08.004] [PMID: 18721898]
[157]
Wong M. A critical review of mTOR inhibitors and epilepsy: from basic science to clinical trials. Expert Rev Neurother 2013; 13(6): 657-69.
[http://dx.doi.org/10.1586/ern.13.48] [PMID: 23739003]
[158]
Zeng LH, Rensing NR, Wong M. The mammalian target of rapamycin signaling pathway mediates epileptogenesis in a model of temporal lobe epilepsy. J Neurosci 2009; 29(21): 6964-72.
[http://dx.doi.org/10.1523/JNEUROSCI.0066-09.2009] [PMID: 19474323]
[159]
Citraro R, Leo A, Constanti A, Russo E, De Sarro G. mTOR pathway inhibition as a new therapeutic strategy in epilepsy and epileptogenesis. Pharmacol Res 2016; 107: 333-43.
[http://dx.doi.org/10.1016/j.phrs.2016.03.039] [PMID: 27049136]
[160]
Vogel KR, Ainslie GR, Schmidt MA, Wisor JP, Gibson KM. mTOR inhibition mitigates molecular and biochemical alterations of vigabatrin-induced visual field toxicity in mice. Pediatr Neurol 2017; 66: 44-52.e1.
[http://dx.doi.org/10.1016/j.pediatrneurol.2016.09.016] [PMID: 27816307]
[161]
Chi X, Huang C, Li R, et al. Inhibition of mTOR pathway by rapamycin decreases P-glycoprotein expression and spontaneous seizures in pharmacoresistant epilepsy. J Mol Neurosci 2017; 61(4): 553-62.
[http://dx.doi.org/10.1007/s12031-017-0897-x] [PMID: 28229367]
[162]
Schneider M, de Vries PJ, Schönig K, Rößner V, Waltereit R. mTOR inhibitor reverses autistic-like social deficit behaviours in adult rats with both Tsc2 haploinsufficiency and developmental status epilepticus. Eur Arch Psychiatry Clin Neurosci 2017; 267(5): 455-63.
[http://dx.doi.org/10.1007/s00406-016-0703-8] [PMID: 27263037]
[163]
Li G, Bauer S, Nowak M, et al. Cytokines and epilepsy. Seizure 2011; 20(3): 249-56.
[http://dx.doi.org/10.1016/j.seizure.2010.12.005] [PMID: 21216630]
[164]
Shimada T, Takemiya T, Sugiura H, Yamagata K. Role of inflammatory mediators in the pathogenesis of epilepsy. Mediators Inflamm 2014; 2014: 901902.
[http://dx.doi.org/10.1155/2014/901902] [PMID: 25197169]
[165]
Cerri C, Caleo M, Bozzi Y. Chemokines as new inflammatory players in the pathogenesis of epilepsy. Epilepsy Res 2017; 136: 77-83.
[http://dx.doi.org/10.1016/j.eplepsyres.2017.07.016] [PMID: 28780154]
[166]
Witte ME, Geurts JJ, de Vries HE, van der Valk P, van Horssen J. Mitochondrial dysfunction: a potential link between neuroinflammation and neurodegeneration? Mitochondrion 2010; 10(5): 411-8.
[http://dx.doi.org/10.1016/j.mito.2010.05.014] [PMID: 20573557]
[167]
Wee Yong V. Inflammation in neurological disorders: a help or a hindrance? Neuroscientist 2010; 16(4): 408-20.
[http://dx.doi.org/10.1177/1073858410371379] [PMID: 20817918]
[168]
McElroy PB, Liang LP, Day BJ, Patel M. Scavenging reactive oxygen species inhibits status epilepticus-induced neuroinflammation. Exp Neurol 2017; 298(Pt A): 13-22.
[http://dx.doi.org/10.1016/j.expneurol.2017.08.009] [PMID: 28822838]
[169]
Meng XF, Tan L, Tan MS, et al. Inhibition of the NLRP3 inflammasome provides neuroprotection in rats following amygdala kindling-induced status epilepticus. J Neuroinflammation 2014; 11: 212.
[http://dx.doi.org/10.1186/s12974-014-0212-5] [PMID: 25516224]
[170]
Zhang XM, Duan RS, Chen Z, et al. IL-18 deficiency aggravates kainic acid-induced hippocampal neurodegeneration in C57BL/6 mice due to an overcompensation by IL-12. Exp Neurol 2007; 205(1): 64-73.
[http://dx.doi.org/10.1016/j.expneurol.2007.01.019] [PMID: 17316614]
[171]
Vezzani A, Maroso M, Balosso S, Sanchez MA, Bartfai T. IL-1 receptor/Toll-like receptor signaling in infection, inflammation, stress and neurodegeneration couples hyperexcitability and seizures. Brain Behav Immun 2011; 25(7): 1281-9.
[http://dx.doi.org/10.1016/j.bbi.2011.03.018] [PMID: 21473909]
[172]
Thawkar BS, Kaur G. Inhibitors of NF-κB and P2X7/NLRP3/Caspase 1 pathway in microglia: Novel therapeutic opportunities in neuroinflammation induced early-stage Alzheimer’s disease. J Neuroimmunol 2019; 326: 62-74.
[http://dx.doi.org/10.1016/j.jneuroim.2018.11.010] [PMID: 30502599]
[173]
Wang S, Yuan YH, Chen NH, Wang HB. The mechanisms of NLRP3 inflammasome/pyroptosis activation and their role in Parkinson’s disease. Int Immunopharmacol 2019; 67: 458-64.
[http://dx.doi.org/10.1016/j.intimp.2018.12.019] [PMID: 30594776]
[174]
Vidmar L, Maver A, Drulović J, et al. Multiple Sclerosis patients carry an increased burden of exceedingly rare genetic variants in the inflammasome regulatory genes. Sci Rep 2019; 9(1): 9171.
[http://dx.doi.org/10.1038/s41598-019-45598-x] [PMID: 31235738]
[175]
Gimenes AD, Andrade BFD, Pinotti JVP, Oliani SM, Galvis-Alonso OY, Gil CD. Annexin A1-derived peptide Ac2-26 in a pilocarpine-induced status epilepticus model: anti-inflammatory and neuroprotective effects. J Neuroinflammation 2019; 16(1): 32.
[http://dx.doi.org/10.1186/s12974-019-1414-7] [PMID: 30755225]
[176]
Azim MS, Agarwal NB, Vohora D. Effects of agomelatine on pentylenetetrazole-induced kindling, kindling-associated oxidative stress, and behavioral despair in mice and modulation of its actions by luzindole and 1-(m-chlorophenyl) piperazine. Epilepsy Behav 2017; 72: 140-4.
[http://dx.doi.org/10.1016/j.yebeh.2017.03.019] [PMID: 28578215]
[177]
Adada M, Canals D, Hannun YA, Obeid LM. Sphingosine-1-phosphate receptor 2. FEBS J 2013; 280(24): 6354-66.
[http://dx.doi.org/10.1111/febs.12446] [PMID: 23879641]
[178]
Edmonds Y, Milstien S, Spiegel S. Development of small-molecule inhibitors of sphingosine-1-phosphate signaling. Pharmacol Ther 2011; 132(3): 352-60.
[http://dx.doi.org/10.1016/j.pharmthera.2011.08.004] [PMID: 21906625]
[179]
Willems LM, Zahn N, Ferreirós N, et al. Sphingosine-1-phosphate receptor inhibition prevents denervation-induced dendritic atrophy. Acta Neuropathol Commun 2016; 4: 28.
[http://dx.doi.org/10.1186/s40478-016-0303-x] [PMID: 27036416]
[180]
O’Sullivan S, Dev KK. Sphingosine-1-phosphate receptor therapies: Advances in clinical trials for CNS-related diseases. Neuropharmacology 2017; 113(Pt B): 597-607.
[http://dx.doi.org/10.1016/j.neuropharm.2016.11.006] [PMID: 27825807]
[181]
Cipriani R, Chara JC, Rodríguez-Antigüedad A, Matute C. Effects of FTY720 on brain neurogenic niches in vitro and after kainic acid-induced injury. J Neuroinflammation 2017; 14(1): 147.
[http://dx.doi.org/10.1186/s12974-017-0922-6] [PMID: 28738875]
[182]
Dong YY, Wang L, Chu X, Cui S, Kong QX. [Altered expressions of SphK1 and S1PR2 in hippocampus of epileptic rats]. Zhongguo Ying Yong Sheng Li Xue Za Zhi 2019; 35(4): 308-11.
[PMID: 31701712]
[183]
Swann JW, Al-Noori S, Jiang M, Lee CL. Spine loss and other dendritic abnormalities in epilepsy. Hippocampus 2000; 10(5): 617-25.
[http://dx.doi.org/10.1002/1098-1063(2000)10:5<617::AID-HIPO13>3.0.CO;2-R] [PMID: 11075833]
[184]
Wong M, Guo D. Dendritic spine pathology in epilepsy: cause or consequence? Neuroscience 2013; 251: 141-50.
[http://dx.doi.org/10.1016/j.neuroscience.2012.03.048] [PMID: 22522469]
[185]
Garris CS, Wu L, Acharya S, et al. Defective sphingosine 1-phosphate receptor 1 (S1P1) phosphorylation exacerbates TH17-mediated autoimmune neuroinflammation. Nat Immunol 2013; 14(11): 1166-72.
[http://dx.doi.org/10.1038/ni.2730] [PMID: 24076635]
[186]
Raza Z, Saleem U, Naureen Z. Sphingosine 1-phosphate signaling in ischemia and reperfusion injury. Prostaglandins Other Lipid Mediat 2020; 149: 106436.
[http://dx.doi.org/10.1016/j.prostaglandins.2020.106436] [PMID: 32173486]
[187]
Leo A, Citraro R, Marra R, et al. The sphingosine 1-phosphate signaling pathway in epilepsy: a possible role for the immunomodulator drug fingolimod in epilepsy treatment. CNS Neurol Disord Drug Targets 2017; 16(3): 311-25.
[http://dx.doi.org/10.2174/1871527315666161104163031] [PMID: 27823573]
[188]
Gao F, Gao Y, Meng F, Yang C, Fu J, Li Y. The sphingosine 1-phosphate analogue FTY720 alleviates seizure-induced overexpression of p-glycoprotein in rat hippocampus. Basic Clin Pharmacol Toxicol 2018; 123(1): 14-20.
[http://dx.doi.org/10.1111/bcpt.12973] [PMID: 29380527]
[189]
Diotel N, Charlier TD, Lefebvre d’Hellencourt C, et al. Steroid transport, local synthesis, and signaling within the brain: roles in neurogenesis, neuroprotection, and sexual behaviors. Front Neurosci 2018; 12: 84.
[http://dx.doi.org/10.3389/fnins.2018.00084] [PMID: 29515356]
[190]
Grube M, Hagen P, Jedlitschky G. Neurosteroid transport in the brain: role of ABC and SLC transporters. Front Pharmacol 2018; 9: 354.
[http://dx.doi.org/10.3389/fphar.2018.00354] [PMID: 29695968]
[191]
Yilmaz C, Karali K, Fodelianaki G, et al. Neurosteroids as regulators of neuroinflammation. Front Neuroendocrinol 2019; 55: 100788.
[http://dx.doi.org/10.1016/j.yfrne.2019.100788] [PMID: 31513776]
[192]
Ratner MH, Kumaresan V, Farb DH. Neurosteroid actions in memory and neurologic/neuropsychiatric disorders. Front Endocrinol (Lausanne) 2019; 10: 169.
[http://dx.doi.org/10.3389/fendo.2019.00169] [PMID: 31024441]
[193]
Grosso S, Luisi S, Mostardini R, et al. Inter-ictal and post-ictal circulating levels of allopregnanolone, an anticonvulsant metabolite of progesterone, in epileptic children. Epilepsy Res 2003; 54(1): 29-34.
[http://dx.doi.org/10.1016/S0920-1211(03)00042-1] [PMID: 12742593]
[194]
Murashima YL, Yoshii M. New therapeutic approaches for epilepsies, focusing on reorganization of the GABAA receptor subunits by neurosteroids. Epilepsia 2010; 51(Suppl. 3): 131-4.
[http://dx.doi.org/10.1111/j.1528-1167.2010.02627.x] [PMID: 20618418]
[195]
Reddy DS. Neurosteroids and their role in sex-specific epilepsies. Neurobiol Dis 2014; 72(Pt B): 198-209.
[http://dx.doi.org/10.1016/j.nbd.2014.06.010] [PMID: 24960208]
[196]
Reddy DS. Role of anticonvulsant and antiepileptogenic neurosteroids in the pathophysiology and treatment of epilepsy. Front Endocrinol (Lausanne) 2011; 2: 38.
[http://dx.doi.org/10.3389/fendo.2011.00038] [PMID: 22654805]
[197]
Biagini G, Rustichelli C, Curia G, et al. Neurosteroids and epileptogenesis. J Neuroendocrinol 2013; 25(11): 980-90.
[http://dx.doi.org/10.1111/jne.12063] [PMID: 23763517]
[198]
Perkins EC, Newport DJ. Neurosteroids in the pathophysiology and treatment of mood and anxiety disorders. Curr Treat Options Psychiatry 2018; 5: 377-400.
[http://dx.doi.org/10.1007/s40501-018-0159-8]
[199]
Valencia-Sanchez C, Crepeau AZ, Hoerth MT, et al. Is adjunctive progesterone effective in reducing seizure frequency in patients with intractable catamenial epilepsy? A critically appraised topic. Neurologist 2018; 23(3): 108-12.
[http://dx.doi.org/10.1097/NRL.0000000000000167] [PMID: 29722747]
[200]
Tesic V, Joksimovic SM, Quillinan N, et al. Neuroactive steroids alphaxalone and CDNC24 are effective hypnotics and potentiators of GABAA currents, but are not neurotoxic to the developing rat brain. Br J Anaesth 2020; 124(5): 603-13.
[http://dx.doi.org/10.1016/j.bja.2020.01.013] [PMID: 32151384]
[201]
Hernández CC, Burgos CF, Gajardo AH, et al. Neuroprotective effects of erythropoietin on neurodegenerative and ischemic brain diseases: the role of erythropoietin receptor. Neural Regen Res 2017; 12(9): 1381-9.
[http://dx.doi.org/10.4103/1673-5374.215240] [PMID: 29089974]
[202]
Habib P, Stamm AS, Zeyen T, et al. EPO regulates neuroprotective Transmembrane BAX Inhibitor-1 Motif-containing (TMBIM) family members GRINA and FAIM2 after cerebral ischemia-reperfusion injury. Exp Neurol 2019; 320: 112978.
[http://dx.doi.org/10.1016/j.expneurol.2019.112978] [PMID: 31211943]
[203]
Bahçekapılı N, Akgün-Dar K, Albeniz I, et al. Erythropoietin pretreatment suppresses seizures and prevents the increase in inflammatory mediators during pentylenetetrazole-induced generalized seizures. Int J Neurosci 2014; 124(10): 762-70.
[http://dx.doi.org/10.3109/00207454.2013.878935] [PMID: 24397543]
[204]
Roseti C, Cifelli P, Ruffolo G, et al. Erythropoietin increases GABAA currents in human cortex from TLE patients Neuroscience 2020; 439: 153-62.
[205]
Nairz M, Sonnweber T, Schroll A, Theurl I, Weiss G. The pleiotropic effects of erythropoietin in infection and inflammation. Microbes Infect 2012; 14(3): 238-46.
[http://dx.doi.org/10.1016/j.micinf.2011.10.005] [PMID: 22094132]
[206]
Ott C, Martens H, Hassouna I, et al. Widespread expression of erythropoietin receptor in brain and its induction by injury. Mol Med 2015; 21(1): 803-15.
[http://dx.doi.org/10.2119/molmed.2015.00192] [PMID: 26349059]
[207]
Castaneda-Arellano R, Beas-Zarate C, Feria-Velasco AI, Bitar-Alatorre EW, Rivera-Cervantes MC. From neurogenesis to neuroprotection in the epilepsy: signalling by erythropoietin. Front Biosci 2014; 19: 1445-55.
[http://dx.doi.org/10.2741/4295] [PMID: 24896364]
[208]
Li Q, Han Y, Du J, et al. Recombinant human erythropoietin protects against hippocampal damage in developing rats with seizures by modulating autophagy via the S6 protein in a time-dependent manner. Neurochem Res 2018; 43(2): 465-76.
[http://dx.doi.org/10.1007/s11064-017-2443-1] [PMID: 29238892]
[209]
Kaspar JW, Jaiswal AK. Antioxidant-induced phosphorylation of tyrosine 486 leads to rapid nuclear export of Bach1 that allows Nrf2 to bind to the antioxidant response element and activate defensive gene expression. J Biol Chem 2010; 285(1): 153-62.
[http://dx.doi.org/10.1074/jbc.M109.040022] [PMID: 19897490]
[210]
Kaspar JW, Jaiswal AK. Tyrosine phosphorylation controls nuclear export of Fyn, allowing Nrf2 activation of cytoprotective gene expression. FASEB J 2011; 25(3): 1076-87.
[http://dx.doi.org/10.1096/fj.10-171553] [PMID: 21097520]
[211]
Kaspar JW, Niture SK, Jaiswal AK. Antioxidant-induced INrf2 (Keap1) tyrosine 85 phosphorylation controls the nuclear export and degradation of the INrf2-Cul3-Rbx1 complex to allow normal Nrf2 activation and repression. J Cell Sci 2012; 125(Pt 4): 1027-38.
[http://dx.doi.org/10.1242/jcs.097295] [PMID: 22448038]
[212]
Ma Q, He X. Molecular basis of electrophilic and oxidative defense: promises and perils of Nrf2. Pharmacol Rev 2012; 64(4): 1055-81.
[http://dx.doi.org/10.1124/pr.110.004333] [PMID: 22966037]
[213]
Ma Q. Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol 2013; 53: 401-26.
[http://dx.doi.org/10.1146/annurev-pharmtox-011112-140320] [PMID: 23294312]
[214]
Petri S, Körner S, Kiaei M. Nrf2/ARE signaling pathway: key mediator in oxidative stress and potential therapeutic target in ALS. Neurol Res Int 2012; 2012: 878030.
[http://dx.doi.org/10.1155/2012/878030] [PMID: 23050144]
[215]
Sandberg M, Patil J, D’Angelo B, Weber SG, Mallard C. NRF2-regulation in brain health and disease: implication of cerebral inflammation. Neuropharmacology 2014; 79: 298-306.
[http://dx.doi.org/10.1016/j.neuropharm.2013.11.004] [PMID: 24262633]
[216]
Kovac S, Dinkova-Kostova AT, Abramov AY. The role of reactive oxygen species in epilepsy. React Oxyg Species (Apex) 2016; 1: 38-52.
[http://dx.doi.org/10.20455/ros.2016.807]
[217]
Shi Y, Miao W, Teng J, Zhang L. Ginsenoside Rb1 protects the brain from damage induced by epileptic seizure via Nrf2/ARE signaling. Cell Physiol Biochem 2018; 45(1): 212-25.
[http://dx.doi.org/10.1159/000486768] [PMID: 29357320]
[218]
Jin M, He Q, Zhang S, Cui Y, Han L, Liu K. Gastrodin suppresses pentylenetetrazole-induced seizures progression by modulating oxidative stress in zebrafish. Neurochem Res 2018; 43(4): 904-17.
[http://dx.doi.org/10.1007/s11064-018-2496-9] [PMID: 29417472]
[219]
Carmona-Aparicio L, Pérez-Cruz C, Zavala-Tecuapetla C, et al. Overview of Nrf2 as therapeutic target in epilepsy. Int J Mol Sci 2015; 16(8): 18348-67.
[http://dx.doi.org/10.3390/ijms160818348] [PMID: 26262608]
[220]
Chen X, Liu J, Chen SY. Sulforaphane protects against ethanol-induced oxidative stress and apoptosis in neural crest cells by the induction of Nrf2-mediated antioxidant response. Br J Pharmacol 2013; 169(2): 437-48.
[http://dx.doi.org/10.1111/bph.12133] [PMID: 23425096]
[221]
Singh S, Singh TG. Role of nuclear factor kappa B (NF-κB) signalling in neurodegenerative diseases: An mechanistic approach. Curr Neuropharmacol 2020; 18: 10-35.: 918-35.
[http://dx.doi.org/10.2174/1570159X18666200207120949] [PMID: 32031074]
[222]
Iqubal A, Sharma S, Najmi AK, et al. Nerolidol ameliorates cyclophosphamide-induced oxidative stress, neuroinflammation and cognitive dysfunction: Plausible role of Nrf2 and NF- κB. Life Sci 2019; 236: 116867.
[http://dx.doi.org/10.1016/j.lfs.2019.116867] [PMID: 31520598]
[223]
Tischkau SA, Mitchell JW, Tyan SH, Buchanan GF, Gillette MU. Ca2+/cAMP Response Element-Binding protein (CREB)-dependent activation of Per1 is required for light-induced signaling in the suprachiasmatic nucleus circadian clock. J Biol Chem 2003; 278(2): 718-23.
[http://dx.doi.org/10.1074/jbc.M209241200] [PMID: 12409294]
[224]
Jancic D, Lopez de Armentia M, Valor LM, Olivares R, Barco A. Inhibition of cAMP response element-binding protein reduces neuronal excitability and plasticity, and triggers neurodegeneration. Cereb Cortex 2009; 19(11): 2535-47.
[http://dx.doi.org/10.1093/cercor/bhp004] [PMID: 19213815]
[225]
Wu G, Yu J, Wang L, Ren S, Zhang Y. PKC/CREB pathway mediates the expressions of GABAA receptor subunits in cultured hippocampal neurons after low-Mg2+ solution treatment. Epilepsy Res 2018; 140: 155-61.
[http://dx.doi.org/10.1016/j.eplepsyres.2017.11.004] [PMID: 29414524]
[226]
Lou Y, Wang WP, Li P, Duan RS, Pei L. Interrelationship between change of cAMP responsive element binding protein (CREB) or N-methyl-D-aspartate receptor (NR1) expressing in hippocampus and impairment of learning and memory after epilepsy. Sichuan Da Xue Xue Bao Yi Xue Ban 2007; 38(6): 949-53.
[PMID: 18095593]
[227]
Sharma P, Sharma S, Singh D. Apigenin reverses behavioural impairments and cognitive decline in kindled mice via CREB-BDNF upregulation in the hippocampus. Nutr Neurosci 2020; 23(2): 118-27.
[http://dx.doi.org/10.1080/1028415X.2018.1478653] [PMID: 29847220]
[228]
Park SA, Kim TS, Choi KS, Park HJ, Heo K, Lee BI. Chronic activation of CREB and p90RSK in human epileptic hippocampus. Exp Mol Med 2003; 35(5): 365-70.
[http://dx.doi.org/10.1038/emm.2003.48] [PMID: 14646589]
[229]
Grabenstatter HL, Russek SJ, Brooks-Kayal AR. Molecular pathways controlling inhibitory receptor expression. Epilepsia 2012; 53(Suppl. 9): 71-8.
[http://dx.doi.org/10.1111/epi.12036] [PMID: 23216580]
[230]
Zhu X, Han X, Blendy JA, Porter BE. Decreased CREB levels suppress epilepsy. Neurobiol Dis 2012; 45(1): 253-63.
[http://dx.doi.org/10.1016/j.nbd.2011.08.009] [PMID: 21867753]
[231]
Guo J, Wang H, Wang Q, Chen Y, Chen S. Expression of p-CREB and activity-dependent miR-132 in temporal lobe epilepsy. Int J Clin Exp Med 2014; 7(5): 1297-306.
[PMID: 24995086]
[232]
Zhu X, Dubey D, Bermudez C, Porter BE. Suppressing cAMP response element-binding protein transcription shortens the duration of status epilepticus and decreases the number of spontaneous seizures in the pilocarpine model of epilepsy. Epilepsia 2015; 56(12): 1870-8.
[http://dx.doi.org/10.1111/epi.13211] [PMID: 26419901]
[233]
Yu J, Liu Z, Wang L, Wu G, Wu M. Increased GABA (A) Receptors alpha1, gamma2, delta Subunits might be Associated with the Activation of the CREB Gene in Low Mg2+ Model of Epilepsy. Neuropsychiatry (London) 2017; 7: 398-405.
[234]
Zhang XM, Zheng XY, Sharkawi SS, et al. Possible protecting role of TNF-α in kainic acid-induced neurotoxicity via down-regulation of NFκB signaling pathway. Curr Alzheimer Res 2013; 10(6): 660-9.
[http://dx.doi.org/10.2174/15672050113109990007] [PMID: 23627756]
[235]
Roopra A, Dingledine R, Hsieh J. Epigenetics and epilepsy. Epilepsia 2012; 53(Suppl. 9): 2-10.
[http://dx.doi.org/10.1111/epi.12030] [PMID: 23216574]
[236]
Hwang JY, Zukin RS. REST, a master transcriptional regulator in neurodegenerative disease. Curr Opin Neurobiol 2018; 48: 193-200.
[http://dx.doi.org/10.1016/j.conb.2017.12.008] [PMID: 29351877]
[237]
Mucha M, Ooi L, Linley JE, et al. Transcriptional control of KCNQ channel genes and the regulation of neuronal excitability. J Neurosci 2010; 30(40): 13235-45.
[http://dx.doi.org/10.1523/JNEUROSCI.1981-10.2010] [PMID: 20926649]
[238]
McClelland S, Brennan GP, Dubé C, et al. The transcription factor NRSF contributes to epileptogenesis by selective repression of a subset of target genes. eLife 2014; 3: e01267.
[http://dx.doi.org/10.7554/eLife.01267] [PMID: 25117540]
[239]
Soysal H, Doğan Z, Kamışlı Ö. Effects of phenytoin and lamotrigine treatment on serum BDNF levels in offsprings of epileptic rats. Neuropeptides 2016; 56: 1-8.
[http://dx.doi.org/10.1016/j.npep.2015.12.001] [PMID: 26706181]
[240]
Sharma A, Kaur G. Tinospora cordifolia as a potential neuroregenerative candidate against glutamate induced excitotoxicity: an in vitro perspective. BMC Complement Altern Med 2018; 18(1): 268.
[http://dx.doi.org/10.1186/s12906-018-2330-6] [PMID: 30285727]
[241]
Nagib MM, Tadros MG, Rahmo RM, Sabri NA, Khalifa AE, Masoud SI. Ameliorative effects of α-tocopherol and/or coenzyme Q10 on phenytoin-induced cognitive impairment in rats: role of VEGF and BDNF-TrkB-CREB pathway. Neurotox Res 2019; 35(2): 451-62.
[http://dx.doi.org/10.1007/s12640-018-9971-6] [PMID: 30374909]
[242]
Martínez-Levy GA, Rocha L, Rodríguez-Pineda F, et al. Increased expression of brain-derived neurotrophic factor transcripts I and VI, cAMP response element binding, and glucocorticoid receptor in the cortex of patients with temporal lobe epilepsy. Mol Neurobiol 2018; 55(5): 3698-708.
[PMID: 28527108]
[243]
Iughetti L, Lucaccioni L, Fugetto F, Predieri B, Berardi A, Ferrari F. Brain-derived neurotrophic factor and epilepsy: a systematic review. Neuropeptides 2018; 72: 23-9.
[http://dx.doi.org/10.1016/j.npep.2018.09.005] [PMID: 30262417]
[244]
Lu B, Nagappan G, Lu Y. BDNF and synaptic plasticity, cognitive function, and dysfunction. Handb Exp Pharmacol 2014; 220: 223-50.
[http://dx.doi.org/10.1007/978-3-642-45106-5_9] [PMID: 24668475]
[245]
Nateri AS, Raivich G, Gebhardt C, et al. ERK activation causes epilepsy by stimulating NMDA receptor activity. EMBO J 2007; 26(23): 4891-901.
[http://dx.doi.org/10.1038/sj.emboj.7601911] [PMID: 17972914]
[246]
de Almeida AA, Gomes da Silva S, Lopim GM, et al. Physical exercise alters the activation of downstream proteins related to BDNF-TrkB signaling in male Wistar rats with epilepsy. J Neurosci Res 2018; 96(5): 911-20.
[http://dx.doi.org/10.1002/jnr.24196] [PMID: 29098710]
[247]
Li Y, Peng Z, Xiao B, Houser CR. Activation of ERK by spontaneous seizures in neural progenitors of the dentate gyrus in a mouse model of epilepsy. Exp Neurol 2010; 224(1): 133-45.
[http://dx.doi.org/10.1016/j.expneurol.2010.03.003] [PMID: 20226181]
[248]
Sivakova N, Lipatova L, Serebryanaya N. The role of neuroinflammation in pathogenesis of epilepsy and the possibility of neuroimmunomodulation. Eur Neuropsychopharmacol 2018; 28: S9-S10.
[http://dx.doi.org/10.1016/j.euroneuro.2017.12.027]
[249]
Yang F, Sun X, Ding Y, et al. Astrocytic acid-sensing ion channel 1a contributes to the development of chronic epileptogenesis. Sci Rep 2016; 6: 1-14.
[http://dx.doi.org/10.1038/srep38593]
[250]
Wu H, Wang C, Liu B, et al. Altered expression pattern of acid-sensing ion channel isoforms in piriform cortex after seizures. Mol Neurobiol 2016; 53(3): 1782-93.
[http://dx.doi.org/10.1007/s12035-015-9130-5] [PMID: 25744567]
[251]
Sun S, Li H, Chen J, Qian Q. Lactic acid: no longer an inert and end-product of glycolysis. Physiology (Bethesda) 2017; 32(6): 453-63.
[http://dx.doi.org/10.1152/physiol.00016.2017] [PMID: 29021365]
[252]
Schurr A. Lactate, not pyruvate, is the end product of glucose metabolism via glycolysis. Carbohydrate 2017; pp. 21-35.
[http://dx.doi.org/10.5772/66699]
[253]
Cao Q, Xiao ZM, Wang X, et al. Inhibition of acid sensing ion channel 3 aggravates seizures by regulating NMDAR function. Neurochem Res 2018; 43(6): 1227-41.
[http://dx.doi.org/10.1007/s11064-018-2540-9] [PMID: 29736613]
[254]
Ortega-Ramírez A, Vega R, Soto E. Acid-sensing ion channels as potential therapeutic targets in neurodegeneration and neuroinflammation. Mediators Inflamm 2017; 2017: 3728096.
[http://dx.doi.org/10.1155/2017/3728096] [PMID: 29056828]
[255]
Fitzwalter BE, Towers CG, Sullivan KD, et al. Autophagy inhibition mediates apoptosis sensitization in cancer therapy by relieving FOXO3a turnover. Dev Cell 2018; 44(5): 555-565.e3.
[http://dx.doi.org/10.1016/j.devcel.2018.02.014] [PMID: 29533771]
[256]
Kim YS, Choi MY, Lee DH, et al. Decreased interaction between FoxO3a and Akt correlates with seizure-induced neuronal death. Epilepsy Res 2014; 108(3): 367-78.
[http://dx.doi.org/10.1016/j.eplepsyres.2014.01.003] [PMID: 24518891]
[257]
Caballero-Caballero A, Engel T, Martinez-Villarreal J, et al. Mitochondrial localization of the forkhead box class O transcription factor FOXO3a in brain. J Neurochem 2013; 124(6): 749-56.
[http://dx.doi.org/10.1111/jnc.12133] [PMID: 23278239]
[258]
Park SH, Sim YB, Lee JK, Lee JY, Suh HW. Characterization of temporal expressions of FOXO and pFOXO proteins in the hippocampus by kainic acid in mice: involvement of NMDA and non-NMDA receptors. Arch Pharm Res 2016; 39(5): 660-7.
[http://dx.doi.org/10.1007/s12272-016-0733-9] [PMID: 26987339]
[259]
de Curtis I. Roles of Rac1 and Rac3 GTPases during the development of cortical and hippocampal GABAergic interneurons. Front Cell Neurosci 2014; 8: 307.
[http://dx.doi.org/10.3389/fncel.2014.00307] [PMID: 25309333]
[260]
Li J, Mi X, Chen L, et al. Dock3 participate in epileptogenesis through rac1 pathway in animal models. Mol Neurobiol 2016; 53(4): 2715-25.
[http://dx.doi.org/10.1007/s12035-015-9406-9] [PMID: 26319681]
[261]
Vaghi V, Pennucci R, Talpo F, et al. Rac1 and rac3 GTPases control synergistically the development of cortical and hippocampal GABAergic interneurons. Cereb Cortex 2014; 24(5): 1247-58.
[http://dx.doi.org/10.1093/cercor/bhs402] [PMID: 23258346]
[262]
Bharti A, Kraeft SK, Gounder M, et al. Inactivation of DNA-dependent protein kinase by protein kinase Cdelta: implications for apoptosis. Mol Cell Biol 1998; 18(11): 6719-28.
[http://dx.doi.org/10.1128/MCB.18.11.6719] [PMID: 9774685]
[263]
Pasparakis M, Vandenabeele P. Necroptosis and its role in inflammation. Nature 2015; 517(7534): 311-20.
[http://dx.doi.org/10.1038/nature14191] [PMID: 25592536]
[264]
Culmsee C, Bondada S, Mattson MP. Hippocampal neurons of mice deficient in DNA-dependent protein kinase exhibit increased vulnerability to DNA damage, oxidative stress and excitotoxicity. Brain Res Mol Brain Res 2001; 87(2): 257-62.
[http://dx.doi.org/10.1016/S0169-328X(01)00008-0] [PMID: 11245929]
[265]
Song J, Hu J, Tanouye M. Seizure suppression by top1 mutations in Drosophila. J Neurosci 2007; 27(11): 2927-37.
[http://dx.doi.org/10.1523/JNEUROSCI.3944-06.2007] [PMID: 17360915]
[266]
Song J, Parker L, Hormozi L, Tanouye MA. DNA topoisomerase I inhibitors ameliorate seizure-like behaviors and paralysis in a Drosophila model of epilepsy. Neuroscience 2008; 156(3): 722-8.
[http://dx.doi.org/10.1016/j.neuroscience.2008.07.024] [PMID: 18703119]
[267]
Roberts DS, Raol YH, Bandyopadhyay S, et al. Egr3 stimulation of GABRA4 promoter activity as a mechanism for seizure-induced up-regulation of GABA(A) receptor α4 subunit expression. Proc Natl Acad Sci USA 2005; 102(33): 11894-9.
[http://dx.doi.org/10.1073/pnas.0501434102] [PMID: 16091474]
[268]
Decker EL, Nehmann N, Kampen E, Eibel H, Zipfel PF, Skerka C. Early Growth Response proteins (EGR) and nuclear factors of activated T cells (NFAT) form heterodimers and regulate proinflammatory cytokine gene expression. Nucleic Acids Res 2003; 31(3): 911-21.
[http://dx.doi.org/10.1093/nar/gkg186] [PMID: 12560487]
[269]
Mo J, Kim CH, Lee D, Sun W, Lee HW, Kim H. Early growth response 1 (Egr-1) directly regulates GABAA receptor α2, α4, and θ subunits in the hippocampus. J Neurochem 2015; 133(4): 489-500.
[http://dx.doi.org/10.1111/jnc.13077] [PMID: 25708312]
[270]
Hu SS, Mei L, Chen JY, Huang ZW, Wu H. Expression of immediate-early genes in the dorsal cochlear nucleus in salicylate-induced tinnitus. Eur Arch Otorhinolaryngol 2016; 273(2): 325-32.
[http://dx.doi.org/10.1007/s00405-014-3479-3] [PMID: 25636249]
[271]
Szyndler J, Maciejak P, Wisłowska-Stanek A, Lehner M, Płaźnik A. Changes in the Egr1 and Arc expression in brain structures of pentylenetetrazole-kindled rats. Pharmacol Rep 2013; 65(2): 368-78.
[http://dx.doi.org/10.1016/S1734-1140(13)71012-0] [PMID: 23744421]
[272]
López-López D, Gómez-Nieto R, Herrero-Turrión MJ, et al. Overexpression of the immediate-early genes Egr1, Egr2, and Egr3 in two strains of rodents susceptible to audiogenic seizures. Epilepsy Behav 2017; 71(Pt B): 226-37.
[http://dx.doi.org/10.1016/j.yebeh.2015.12.020] [PMID: 26775236]
[273]
Amada N, Yamasaki Y, Williams CM, Whalley BJ. Cannabidivarin (CBDV) suppresses pentylenetetrazole (PTZ)-induced increases in epilepsy-related gene expression. PeerJ 2013; 1: e214.
[http://dx.doi.org/10.7717/peerj.214] [PMID: 24282673]
[274]
Roberts DS, Hu Y, Lund IV, Brooks-Kayal AR, Russek SJ. BDNF-induced synthesis of early growth response factor 3 (EGR3) controls the levels of type a GABA receptor α4 subunits in hippocampal neurons. J Biol Chem 2006; 281: 29431-5.
[http://dx.doi.org/10.1074/jbc.C600167200] [PMID: 16901909]
[275]
Bauer CK, Schwarz JR. Ether-à-go-go K+ channels: effective modulators of neuronal excitability. J Physiol 2018; 596(5): 769-83.
[http://dx.doi.org/10.1113/JP275477] [PMID: 29333676]
[276]
Haitin Y, Carlson AE, Zagotta WN. The structural mechanism of KCNH-channel regulation by the eag domain. Nature 2013; 501(7467): 444-8.
[http://dx.doi.org/10.1038/nature12487] [PMID: 23975098]
[277]
Xiao K, Sun Z, Jin X, et al. ERG3 potassium channel-mediated suppression of neuronal intrinsic excitability and prevention of seizure generation in mice. J Physiol 2018; 596(19): 4729-52.
[http://dx.doi.org/10.1113/JP275970] [PMID: 30016551]
[278]
Zhang Y, Fang J, Feng W, Sun Q, Xu J, Xia Q. The role of the GLP-1/GLP-1R signaling pathway in regulating seizure susceptibility in rats. Brain Res Bull 2018; 142: 47-53.
[http://dx.doi.org/10.1016/j.brainresbull.2018.06.017] [PMID: 29959973]
[279]
Koshal P, Jamwal S, Kumar P. Glucagon-like Peptide-1 (GLP-1) and neurotransmitters signaling in epilepsy: An insight review. Neuropharmacology 2018; 136(Pt B): 271-9.
[http://dx.doi.org/10.1016/j.neuropharm.2017.11.015] [PMID: 29129776]
[280]
Anderberg RH, Richard JE, Hansson C, Nissbrandt H, Bergquist F, Skibicka KP. GLP-1 is both anxiogenic and antidepressant; divergent effects of acute and chronic GLP-1 on emotionality. Psychoneuroendocrinology 2016; 65: 54-66.
[http://dx.doi.org/10.1016/j.psyneuen.2015.11.021] [PMID: 26724568]
[281]
Willemsen R. Fragile X syndrome, the search for a targeted treatment. J Biomed and Trans Res 2019; 5: 12-4.
[http://dx.doi.org/10.14710/jbtr.v5i1.3925]
[282]
Berry-Kravis E. Epilepsy in fragile X syndrome. Dev Med Child Neurol 2002; 44(11): 724-8.
[http://dx.doi.org/10.1111/j.1469-8749.2002.tb00277.x] [PMID: 12418611]
[283]
Hagerman PJ, Stafstrom CE. Origins of epilepsy in fragile X syndrome. Epilepsy Curr 2009; 9(4): 108-12.
[http://dx.doi.org/10.1111/j.1535-7511.2009.01309.x] [PMID: 19693328]
[284]
Zhang Y, Bonnan A, Bony G, et al. Dendritic channelopathies contribute to neocortical and sensory hyperexcitability in Fmr1(-/y) mice. Nat Neurosci 2014; 17(12): 1701-9.
[http://dx.doi.org/10.1038/nn.3864] [PMID: 25383903]
[285]
Zhang W, Xu C, Tu H, et al. GABAB receptor upregulates fragile X mental retardation protein expression in neurons. Sci Rep 2015; 5: 10468.
[http://dx.doi.org/10.1038/srep10468] [PMID: 26020477]
[286]
Grainger A. Difficulties in tracking the long-term global trend in tropical forest area. Proc Natl Acad Sci USA 2008; 105(2): 818-23.
[http://dx.doi.org/10.1073/pnas.0703015105] [PMID: 18184819]
[287]
Busch RM, Frazier T, Chapin JS, et al. Role of cortisol in mood and memory in patients with intractable temporal lobe epilepsy. Neurology 2012; 78(14): 1064-8.
[http://dx.doi.org/10.1212/WNL.0b013e31824e8efb] [PMID: 22442430]
[288]
Galimberti CA, Magri F, Copello F, et al. Seizure frequency and cortisol and dehydroepiandrosterone sulfate (DHEAS) levels in women with epilepsy receiving antiepileptic drug treatment. Epilepsia 2005; 46(4): 517-23.
[http://dx.doi.org/10.1111/j.0013-9580.2005.59704.x] [PMID: 15816945]
[289]
Maguire J, Salpekar JA. Stress, seizures, and hypothalamic-pituitary-adrenal axis targets for the treatment of epilepsy. Epilepsy Behav 2013; 26(3): 352-62.
[http://dx.doi.org/10.1016/j.yebeh.2012.09.040] [PMID: 23200771]
[290]
Tolmacheva EA, Oitzl MS, van Luijtelaar G. Stress, glucocorticoids and absences in a genetic epilepsy model. Horm Behav 2012; 61(5): 706-10.
[http://dx.doi.org/10.1016/j.yhbeh.2012.03.004] [PMID: 22465594]
[291]
Pineda E, Shin D, Sankar R, Mazarati AM. Comorbidity between epilepsy and depression: experimental evidence for the involvement of serotonergic, glucocorticoid, and neuroinflammatory mechanisms. Epilepsia 2010; 51(Suppl. 3): 110-4.
[http://dx.doi.org/10.1111/j.1528-1167.2010.02623.x] [PMID: 20618414]
[292]
Gomes BAQ, Silva JPB, Romeiro CFR, et al. Neuroprotective mechanisms of resveratrol in Alzheimer’s disease: role of SIRT1. Oxid Med Cell Longev 2018; 2018: 8152373.
[http://dx.doi.org/10.1155/2018/8152373] [PMID: 30510627]
[293]
Zhou Y, Wang S, Li Y, Yu S, Zhao Y. SIRT1/PGC-1α signaling promotes mitochondrial functional recovery and reduces apoptosis after intracerebral hemorrhage in rats. Front Mol Neurosci 2018; 10: 443.
[http://dx.doi.org/10.3389/fnmol.2017.00443] [PMID: 29375306]
[294]
Zeng XX, Deng J, Xiang J, et al. Resveratrol attenuated the increased level of oxidative stress in the brains and the deficit of learning and memory of rats with chronic fluorosis. Fluoride 2019; 52: 149-60.
[295]
Chuang YC, Chen SD, Jou SB, et al. Sirtuin 1 regulates mitochondrial biogenesis and provides an endogenous neuroprotective mechanism against seizure-induced neuronal cell death in the hippocampus following status epilepticus. Int J Mol Sci 2019; 20(14): 3588.
[http://dx.doi.org/10.3390/ijms20143588] [PMID: 31340436]
[296]
Mohar DS, Malik S. The sirtuin system: the holy grail of resveratrol? J Clin Exp Cardiolog 2012; 3(11): 216.
[http://dx.doi.org/10.4172/2155-9880.1000216] [PMID: 23560248]
[297]
Chen Y, Xie Y, Wang H, Chen Y. SIRT1 expression and activity are up-regulated in the brain tissue of epileptic patients and rat models. Nan Fang Yi Ke Da Xue Xue Bao 2013; 33(4): 528-32.
[PMID: 23644113]
[298]
Maugeri A, Barchitta M, Mazzone MG, Giuliano F, Basile G, Agodi A. Resveratrol modulates SIRT1 and DNMT functions and restores LINE-1 methylation levels in ARPE-19 cells under oxidative stress and inflammation. Int J Mol Sci 2018; 19(7): 2118.
[http://dx.doi.org/10.3390/ijms19072118] [PMID: 30037017]
[299]
Truong VL, Jun M, Jeong WS. Role of resveratrol in regulation of cellular defense systems against oxidative stress. Biofactors 2018; 44(1): 36-49.
[http://dx.doi.org/10.1002/biof.1399] [PMID: 29193412]
[300]
Pallàs M, Ortuño-Sahagún D, Andrés-Benito P, Ponce-Regalado MD, Rojas-Mayorquín AE. Resveratrol in epilepsy: preventive or treatment opportunities? Front Biosci 2014; 19: 1057-64.
[http://dx.doi.org/10.2741/4267] [PMID: 24896336]
[301]
Musto AE, Gjorstrup P, Bazan NG. The omega-3 fatty acid-derived neuroprotectin D1 limits hippocampal hyperexcitability and seizure susceptibility in kindling epileptogenesis. Epilepsia 2011; 52(9): 1601-8.
[http://dx.doi.org/10.1111/j.1528-1167.2011.03081.x] [PMID: 21569016]
[302]
Fassio A, Raimondi A, Lignani G, Benfenati F, Baldelli P. Synapsins: from synapse to network hyperexcitability and epilepsy. Semin Cell Dev Biol 2011; 22(4): 408-15.
[http://dx.doi.org/10.1016/j.semcdb.2011.07.005] [PMID: 21816229]
[303]
Krishnakumar A, Anju TR, Abraham PM, Paulose CS. Alteration in 5-HT-C, NMDA receptor and IP3 in cerebral cortex of epileptic rats: restorative role of Bacopa monnieri. Neurochem Res 2015; 40(1): 216-25.
[http://dx.doi.org/10.1007/s11064-014-1472-2] [PMID: 25503823]
[304]
Hall AM, Brennan GP, Nguyen TM, et al. The role of Sirt1 in epileptogenesis. eNeuro 2017; 4(1): 4.
[http://dx.doi.org/10.1523/ENEURO.0301-16.2017] [PMID: 28197553]
[305]
Chindo BA, Anuka JA, McNeil L, et al. Anticonvulsant properties of saponins from Ficus platyphylla stem bark. Brain Res Bull 2009; 78(6): 276-82.
[http://dx.doi.org/10.1016/j.brainresbull.2008.12.005] [PMID: 19111909]
[306]
Galtrey CM, Fawcett JW. The role of chondroitin sulfate proteoglycans in regeneration and plasticity in the central nervous system. Brain Res Brain Res Rev 2007; 54(1): 1-18.
[http://dx.doi.org/10.1016/j.brainresrev.2006.09.006] [PMID: 17222456]
[307]
DeGiorgio CM, Taha AY. Omega-3 fatty acids (ῳ-3 fatty acids) in epilepsy: animal models and human clinical trials. Expert Rev Neurother 2016; 16(10): 1141-5.
[http://dx.doi.org/10.1080/14737175.2016.1226135] [PMID: 27534261]
[308]
Binder DK, Nagelhus EA, Ottersen OP. Aquaporin-4 and epilepsy. Glia 2012; 60(8): 1203-14.
[http://dx.doi.org/10.1002/glia.22317] [PMID: 22378467]
[309]
Nagelhus EA, Mathiisen TM, Ottersen OP. Aquaporin-4 in the central nervous system: cellular and subcellular distribution and coexpression with KIR4.1. Neuroscience 2004; 129(4): 905-13.
[http://dx.doi.org/10.1016/j.neuroscience.2004.08.053] [PMID: 15561407]
[310]
Bienvenu E, Amabeoku GJ, Eagles PK, Scott G, Springfield EP. Anticonvulsant activity of aqueous extract of Leonotis leonurus. Phytomedicine 2002; 9(3): 217-23.
[http://dx.doi.org/10.1078/0944-7113-00103] [PMID: 12046862]
[311]
Fornasiero EF, Bonanomi D, Benfenati F, Valtorta F. The role of synapsins in neuronal development. Cell Mol Life Sci 2010; 67(9): 1383-96.
[http://dx.doi.org/10.1007/s00018-009-0227-8] [PMID: 20035364]
[312]
Ibrahim FAS, Ghebremeskel K, Abdel-Rahman ME, et al. The differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on seizure frequency in patients with drug-resistant epilepsy - A randomized, double-blind, placebo-controlled trial. Epilepsy Behav 2018; 87: 32-8.
[http://dx.doi.org/10.1016/j.yebeh.2018.08.016] [PMID: 30170260]
[313]
Paonessa F, Latifi S, Scarongella H, Cesca F, Benfenati F. Specificity protein 1 (Sp1)-dependent activation of the synapsin I gene (SYN1) is modulated by RE1-silencing transcription factor (REST) and 5′-cytosine-phosphoguanine (CpG) methylation. J Biol Chem 2013; 288(5): 3227-39.
[http://dx.doi.org/10.1074/jbc.M112.399782] [PMID: 23250796]
[314]
Lignani G, Raimondi A, Ferrea E, et al. Epileptogenic Q555X SYN1 mutant triggers imbalances in release dynamics and short-term plasticity. Hum Mol Genet 2013; 22(11): 2186-99.
[http://dx.doi.org/10.1093/hmg/ddt071] [PMID: 23406870]
[315]
Brennan GP, Dey D, Chen Y, et al. Dual and opposing roles of microRNA-124 in epilepsy are mediated through inflammatory and NRSF-dependent gene networks. Cell Rep 2016; 14(10): 2402-12.
[http://dx.doi.org/10.1016/j.celrep.2016.02.042] [PMID: 26947066]
[316]
Ngoupaye GT, Ngo Bum E, Ngah E, et al. The anticonvulsant and sedative effects of Gladiolus dalenii extracts in mice. Epilepsy Behav 2013; 28(3): 450-6.
[http://dx.doi.org/10.1016/j.yebeh.2013.06.014] [PMID: 23891766]
[317]
Park HG, Yoon SY, Choi JY, et al. Anticonvulsant effect of wogonin isolated from Scutellaria baicalensis. Eur J Pharmacol 2007; 574(2-3): 112-9.
[http://dx.doi.org/10.1016/j.ejphar.2007.07.011] [PMID: 17692312]
[318]
Sharma H, Garg M. A review of traditional use, phytoconstituents and biological activities of Himalayan yew, Taxus wallichiana. J Integr Med 2015; 13(2): 80-90.
[http://dx.doi.org/10.1016/S2095-4964(15)60161-3] [PMID: 25797638]
[319]
Tang H, Shao C, He J. Down-regulated expression of aquaporin-4 in the cerebellum after status epilepticus. Cogn Neurodyn 2017; 11(2): 183-8.
[http://dx.doi.org/10.1007/s11571-016-9420-2] [PMID: 28348649]
[320]
Mahomed IM, Ojewole JA. Anticonvulsant activity of Harpagophytum procumbens DC [Pedaliaceae] secondary root aqueous extract in mice. Brain Res Bull 2006; 69(1): 57-62.
[http://dx.doi.org/10.1016/j.brainresbull.2005.10.010] [PMID: 16464685]
[321]
Hubbard JA, Hsu MS, Seldin MM, Binder DK. Expression of the astrocyte water channel aquaporin-4 in the mouse brain. ASN Neuro 2015; 7(5): 1759091415605486.
[http://dx.doi.org/10.1177/1759091415605486] [PMID: 26489685]
[322]
Su J, Liu J, Yan XY, et al. Cytoprotective effect of the UCP2-SIRT3 signaling pathway by decreasing mitochondrial oxidative stress on cerebral ischemia–reperfusion injury. Int J Mol Sci 2017; 18(7): 1599.
[http://dx.doi.org/10.3390/ijms18071599] [PMID: 28737710]
[323]
Thomas J, Thomas CJ, Radcliffe J, Itsiopoulos C. Omega-3 fatty acids in early prevention of inflammatory neurodegenerative disease: a focus on Alzheimer’s disease. BioMed Res Int 2015; 2015: 172801.
[http://dx.doi.org/10.1155/2015/172801] [PMID: 26301243]
[324]
Hubbard JA, Szu JI, Binder DK. The role of aquaporin-4 in synaptic plasticity, memory and disease. Brain Res Bull 2018; 136: 118-29.
[http://dx.doi.org/10.1016/j.brainresbull.2017.02.011] [PMID: 28274814]
[325]
Ojewole JA. Anticonvulsant property of Sutherlandia frutescens R. BR. (variety Incana E. MEY.) [Fabaceae] shoot aqueous extract. Brain Res Bull 2008; 75(1): 126-32.
[http://dx.doi.org/10.1016/j.brainresbull.2007.08.002] [PMID: 18158106]
[326]
Mathew J, Balakrishnan S, Antony S, Abraham P M, Paulose C S. Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A J Biom Sci 2012.
[327]
Garba K, Yaro AH, Ya’u J. Anticonvulsant effects of ethanol stem bark extract of Lannea barteri (Anacardiaceae) in mice and chicks. J Ethnopharmacol 2015; 172: 227-31.
[http://dx.doi.org/10.1016/j.jep.2015.06.039] [PMID: 26129937]
[328]
Hu L, Zhang S, Wen H, et al. Melatonin decreases M1 polarization via attenuating mitochondrial oxidative damage depending on UCP2 pathway in prorenin-treated microglia. PLoS One 2019; 14(2): e0212138.
[http://dx.doi.org/10.1371/journal.pone.0212138] [PMID: 30742657]
[329]
Ahmad M, Yaseen M, Bhat A, et al. Taxus wallichiana as a Potential in vitro antioxidant with good lethal effect on pathogenic bactarial strains. Am J Phytomed Clin Ther 2015; 3(3): 209-21.
[330]
Nagib MM, Tadros MG, Al-Khalek HAA, et al. Molecular mechanisms of neuroprotective effect of adjuvant therapy with phenytoin in pentylenetetrazole-induced seizures: Impact on Sirt1/NRF2 signaling pathways. Neurotoxicology 2018; 68: 47-65.
[http://dx.doi.org/10.1016/j.neuro.2018.07.006] [PMID: 30017425]
[331]
Nisar M, Khan I, Simjee SU, Gilani AH, Obaidullah , Perveen H. Anticonvulsant, analgesic and antipyretic activities of Taxus wallichiana Zucc. J Ethnopharmacol 2008; 116(3): 490-4.
[http://dx.doi.org/10.1016/j.jep.2007.12.021] [PMID: 18308491]
[332]
Pahuja M, Mehla J, Reeta KH, Joshi S, Gupta YK. Root extract of Anacyclus pyrethrum ameliorates seizures, seizure-induced oxidative stress and cognitive impairment in experimental animals. Epilepsy Res 2012; 98(2-3): 157-65.
[http://dx.doi.org/10.1016/j.eplepsyres.2011.09.006] [PMID: 21993359]
[333]
Raza M, Shaheen F, Choudhary MI, et al. Anticonvulsant effect of FS-1 subfraction isolated from roots of Delphinim denudatum on hippocampal pyramidal neurons. Phytother Res 2003; 17(1): 38-43.
[http://dx.doi.org/10.1002/ptr.1072] [PMID: 12557245]
[334]
Sayyah M, Valizadeh J, Kamalinejad M. Anticonvulsant activity of the leaf essential oil of Laurus nobilis against pentylenetetrazole- and maximal electroshock-induced seizures. Phytomedicine 2002; 9(3): 212-6.
[http://dx.doi.org/10.1078/0944-7113-00113] [PMID: 12046861]
[335]
Yutsudo N, Kitagawa H. Involvement of chondroitin 6-sulfation in temporal lobe epilepsy. Exp Neurol 2015; 274(Pt B): 126-33.
[http://dx.doi.org/10.1016/j.expneurol.2015.07.009] [PMID: 26231575]
[336]
Toader O, Forte N, Orlando M, et al. Dentate gyrus network dysfunctions precede the symptomatic phase in a genetic mouse model of seizures. Front Cell Neurosci 2013; 7: 138.
[http://dx.doi.org/10.3389/fncel.2013.00138] [PMID: 24009558]
[337]
Casillas-Espinosa PM, Powell KL, O’Brien TJ. Regulators of synaptic transmission: roles in the pathogenesis and treatment of epilepsy. Epilepsia 2012; 53(Suppl. 9): 41-58.
[http://dx.doi.org/10.1111/epi.12034] [PMID: 23216578]
[338]
Miao QL, Ye Q, Zhang XH. Perineuronal net, CSPG receptor and their regulation of neural plasticity. Sheng Li Xue Bao 2014; 66(4): 387-97.
[PMID: 25131780]
[339]
Barbieri R, Contestabile A, Ciardo MG, et al. Synapsin I and Synapsin II regulate neurogenesis in the dentate gyrus of adult mice. Oncotarget 2018; 9(27): 18760-74.
[http://dx.doi.org/10.18632/oncotarget.24655] [PMID: 29721159]
[340]
Mailloux RJ, Harper ME. Uncoupling proteins and the control of mitochondrial reactive oxygen species production. Free Radic Biol Med 2011; 51(6): 1106-15.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.06.022] [PMID: 21762777]
[341]
Kumar R, Arora R, Agarwal A, Gupta YK. Protective effect of Terminalia chebula against seizures, seizure-induced cognitive impairment and oxidative stress in experimental models of seizures in rats. J Ethnopharmacol 2018; 215: 124-31.
[http://dx.doi.org/10.1016/j.jep.2017.12.008] [PMID: 29248452]
[342]
Zhao RZ, Jiang S, Zhang L, Yu ZB. Mitochondrial electron transport chain, ROS generation and uncoupling (Review). Int J Mol Med 2019; 44(1): 3-15.
[http://dx.doi.org/10.3892/ijmm.2019.4188] [PMID: 31115493]
[343]
Nielsen S, Nagelhus EA, Amiry-Moghaddam M, Bourque C, Agre P, Ottersen OP. Specialized membrane domains for water transport in glial cells: high-resolution immunogold cytochemistry of aquaporin-4 in rat brain. J Neurosci 1997; 17(1): 171-80.
[http://dx.doi.org/10.1523/JNEUROSCI.17-01-00171.1997] [PMID: 8987746]
[344]
Tejada S, Martorell M, Capó X, Tur JA, Pons A, Sureda A. J.; Pons, A.; Sureda, A. Omega-3 fatty acids in the management of epilepsy. Curr Top Med Chem 2016; 16(17): 1897-905.
[http://dx.doi.org/10.2174/1568026616666160204123107] [PMID: 26845549]
[345]
Soleman S, Filippov MA, Dityatev A, Fawcett JW. Targeting the neural extracellular matrix in neurological disorders. Neuroscience 2013; 253: 194-213.
[http://dx.doi.org/10.1016/j.neuroscience.2013.08.050] [PMID: 24012743]
[346]
Soman S, Anju TR, Jayanarayanan S, Antony S, Paulose CS. Impaired motor learning attributed to altered AMPA receptor function in the cerebellum of rats with temporal lobe epilepsy: ameliorating effects of Withania somnifera and withanolide A. Epilepsy Behav 2013; 27(3): 484-91.
[http://dx.doi.org/10.1016/j.yebeh.2013.01.007] [PMID: 23602240]
[347]
Ishihara Y, Itoh K, Tanaka M, et al. Potentiation of 17β-estradiol synthesis in the brain and elongation of seizure latency through dietary supplementation with docosahexaenoic acid. Sci Rep 2017; 7: 1-11.
[http://dx.doi.org/10.1038/s41598-017-06630-0]
[348]
Tan Y, Ren H, Shi Z, et al. Endogenous docosahexaenoic acid (dha) prevents aβ1–42 oligomer-induced neuronal injury. Mol Neurobiol 2016; 53(5): 3146-53.
[http://dx.doi.org/10.1007/s12035-015-9224-0] [PMID: 26021747]
[349]
Ding Y, Zheng Y, Huang J, et al. UCP2 ameliorates mitochondrial dysfunction, inflammation, and oxidative stress in lipopolysaccharide-induced acute kidney injury. Int Immunopharmacol 2019; 71: 336-49.
[http://dx.doi.org/10.1016/j.intimp.2019.03.043] [PMID: 30952098]
[350]
Teng Z, Wang A, Wang P, Wang R, Wang W, Han H. The effect of aquaporin-4 knockout on interstitial fluid flow and the structure of the extracellular space in the deep brain. Aging Dis 2018; 9(5): 808-16.
[http://dx.doi.org/10.14336/AD.2017.1115] [PMID: 30271658]
[351]
Tiwari D, Peariso K, Gross C. MicroRNA-induced silencing in epilepsy: Opportunities and challenges for clinical application. Dev Dyn 2018; 247(1): 94-110.
[http://dx.doi.org/10.1002/dvdy.24582] [PMID: 28850760]
[352]
Reschke CR, Silva LFA, Norwood BA, et al. Potent anti-seizure effects of locked nucleic acid antagomirs targeting miR-134 in multiple mouse and rat models of epilepsy. Mol Ther Nucleic Acids 2017; 6: 45-56.
[http://dx.doi.org/10.1016/j.omtn.2016.11.002] [PMID: 28325299]
[353]
Hauser RM, Henshall DC, Lubin FD. The epigenetics of epilepsy and its progression. Neuroscientist 2018; 24(2): 186-200.
[http://dx.doi.org/10.1177/1073858417705840] [PMID: 28468530]
[354]
Bielefeld P, Mooney C, Henshall DC, Fitzsimons CP. miRNA-mediated regulation of adult hippocampal neurogenesis; implications for epilepsy. Brain Plast 2017; 3(1): 43-59.
[http://dx.doi.org/10.3233/BPL-160036] [PMID: 29765859]
[355]
Ma Y. The challenge of microRNA as a biomarker of epilepsy. Curr Neuropharmacol 2018; 16(1): 37-42.
[PMID: 28676013]
[356]
Morris G, Reschke CR, Henshall DC. Targeting microRNA-134 for seizure control and disease modification in epilepsy. EBioMedicine 2019; 45: 646-54.
[http://dx.doi.org/10.1016/j.ebiom.2019.07.008] [PMID: 31300345]
[357]
Qian Y, Song J, Ouyang Y, et al. Advances in roles of miR-132 in the nervous system. Front Pharmacol 2017; 8: 770.
[http://dx.doi.org/10.3389/fphar.2017.00770] [PMID: 29118714]
[358]
Li T R, Jia Y J, Ma C, et al. The role of the microRNA-146a/complement factor H/interleukin-1β-mediated inflammatory loop circuit in the perpetuate inflammation of chronic temporal lobe epilepsy Dise Model Mech 2018; 11
[359]
Tiwari D, Brager DH, Rymer JK, et al. MicroRNA inhibition upregulates hippocampal A-type potassium current and reduces seizure frequency in a mouse model of epilepsy. Neurobiol Dis 2019; 130: 104508.
[http://dx.doi.org/10.1016/j.nbd.2019.104508] [PMID: 31212067]
[360]
Duan W, Chen Y, Wang XR. MicroRNA‑155 contributes to the occurrence of epilepsy through the PI3K/Akt/mTOR signaling pathway. Int J Mol Med 2018; 42(3): 1577-84.
[http://dx.doi.org/10.3892/ijmm.2018.3711] [PMID: 29901097]
[361]
Danis B, van Rikxoort M, Kretschmann A, et al. Differential expression of miR-184 in temporal lobe epilepsy patients with and without hippocampal sclerosis - Influence on microglial function. Sci Rep 2016; 6: 33943.
[http://dx.doi.org/10.1038/srep33943] [PMID: 27666871]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy