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Research progress on oxidative stress regulating different types of neuronal death caused by epileptic seizures

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Abstract

Clinical and experimental data hints that prolonged and repeated epileptic seizures can lead to molecular, biochemical, metabolic, and structural changes in the brain, a continuous process of chronic brain injury that ultimately leads to neuronal death. The histological characteristics of hippocampal structure determine its high sensitivity to excitotoxicity and present different types of neuronal death, including apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis. Hippocampal neuronal death promotes the progression of epileptogenesis, seizures, and epilepsy and is closely related to the impairment of cognitive function. Massive evidence indicates that oxidative stress plays a critical role in different forms of neuronal death induced by epileptic seizures. The brain is particularly vulnerable to damage caused by oxidative stress, and an increase in oxidative stress biomarkers was found in various epilepsy types. The purpose of this review is to elucidate the molecular mechanism of neuronal death and explore the moderating effect of oxidative stress on epileptic seizure-induced neuronal death patterns so as to find potential intervention targets for neuroprotective treatment after epileptic seizures.

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References

  1. Thijs RD, Surges R, O’Brien TJ et al (2019) Epilepsy in adults [J]. Lancet 393(10172):689–701

    Article  PubMed  Google Scholar 

  2. Golyala A, Kwan P (2017) Drug development for refractory epilepsy: the past 25 years and beyond [J]. Seizure 44:147–156

    Article  PubMed  Google Scholar 

  3. Kovac S, Dinkova Kostova AT, Herrmann AM et al (2017) Metabolic and Homeostatic changes in seizures and acquired epilepsy-mitochondria, calcium dynamics and reactive oxygen species [J]. Int J Mol Sci 18(9)

  4. Mao X-Y, Zhou H-H, Jin W-L (2019) Redox-related neuronal death and crosstalk as drug targets: focus on epilepsy [J]. Front Neurosci 13:512

    Article  PubMed  PubMed Central  Google Scholar 

  5. Cai Y, Yang Z (2021) Ferroptosis and its role in epilepsy [J]. Front Cell Neurosci 15:696889

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Gan J, Qu Y, Li J et al (2015) An evaluation of the links between microRNA, autophagy, and epilepsy [J]. Rev Neurosci 26(2):225–237

    Article  CAS  PubMed  Google Scholar 

  7. Geronzi U, Lotti F, Grosso S (2018) Oxidative stress in epilepsy [J]. Expert Rev Neurother 18(5):427–434

    Article  CAS  PubMed  Google Scholar 

  8. Shekh-Ahmad T, Kovac S, Abramov AY et al (2019) Reactive oxygen species in status epilepticus [J]. Epilepsy Behav 101(Pt B):106410

    Article  CAS  PubMed  Google Scholar 

  9. Busceti CL, Biagioni F, Aronica E et al (2007) Induction of the Wnt inhibitor, Dickkopf-1, is associated with neurodegeneration related to temporal lobe epilepsy [J]. Epilepsia 48(4):694–705

    Article  CAS  PubMed  Google Scholar 

  10. Santos VR, Melo IS, Pacheco ALD et al (2021) Life and death in the hippocampus: what’s bad? [J]. Epilepsy Behav 121(Pt B):106595

    Article  PubMed  Google Scholar 

  11. Méndez-Armenta M, Nava-Ruíz C, Juárez-Rebollar D et al (2014) Oxidative stress associated with neuronal apoptosis in experimental models of epilepsy [J]. Oxid Med Cell Longev 2014:293689

    Article  PubMed  PubMed Central  Google Scholar 

  12. Liu J, Wang A, Li L et al (2010) Oxidative stress mediates hippocampal neuron death in rats after lithium-pilocarpine-induced status epilepticus [J]. Seizure 19(3):165–172

    Article  CAS  PubMed  Google Scholar 

  13. Castro OW, Furtado MA, Tilelli CQ et al (2011) Comparative neuroanatomical and temporal characterization of FluoroJade-positive neurodegeneration after status epilepticus induced by systemic and intrahippocampal pilocarpine in Wistar rats [J]. Brain Res 1374:43–55

    Article  CAS  PubMed  Google Scholar 

  14. Wang L, Liu Y-H, Huang Y-G et al (2008) Time-course of neuronal death in the mouse pilocarpine model of chronic epilepsy using Fluoro-Jade C staining [J]. Brain Res 1241:157–67

    Article  CAS  PubMed  Google Scholar 

  15. Sharma AK, Jordan WH, Reams RY et al (2008) Temporal profile of clinical signs and histopathologic changes in an F-344 rat model of kainic acid-induced mesial temporal lobe epilepsy [J]. Toxicol Pathol 36(7):932–943

    Article  PubMed  Google Scholar 

  16. Pang CC-C, Kiecker C, O’Brien JT et al (2019) Ammon’s Horn 2 (CA2) of the hippocampus: a long-known region with a new potential role in neurodegeneration [J]. Neuroscientist 25(2):167–80

    Article  CAS  PubMed  Google Scholar 

  17. Scharfman HE (2018) Advances in understanding hilar mossy cells of the dentate gyrus [J]. Cell Tissue Res 373(3):643–652

    Article  CAS  PubMed  Google Scholar 

  18. Scharfman HE, Myers CE (2012) Hilar mossy cells of the dentate gyrus: a historical perspective [J]. Front Neural Circuits 6:106

    PubMed  Google Scholar 

  19. Alkadhi KA (2019) Cellular and molecular differences between area CA1 and the dentate gyrus of the hippocampus [J]. Mol Neurobiol 56(9):6566–6580

    Article  CAS  PubMed  Google Scholar 

  20. Senzai Y (2019) Function of local circuits in the hippocampal dentate gyrus-CA3 system [J]. Neurosci Res 140:43–52

    Article  PubMed  Google Scholar 

  21. Ambrogini P, Torquato P, Bartolini D et al (2019) Excitotoxicity, neuroinflammation and oxidant stress as molecular bases of epileptogenesis and epilepsy-derived neurodegeneration: the role of vitamin E [J]. Biochim Biophys Acta Mol Basis Dis 1865(6):1098–1112

    Article  CAS  PubMed  Google Scholar 

  22. Wondolowski J, Frerking M (2009) Subunit-dependent postsynaptic expression of kainate receptors on hippocampal interneurons in area CA1 [J]. J Neurosci 29(2):563–574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Martens U, Capito B, Wree A (1998) Septotemporal distribution of [3H]MK-801, [3H]AMPA and [3H]Kainate binding sites in the rat hippocampus [J]. Anat Embryol (Berl) 198(3):195–204

    Article  CAS  Google Scholar 

  24. Meldrum BS (1993) Excitotoxicity and selective neuronal loss in epilepsy [J]. Brain Pathol 3(4):405–412

    Article  CAS  PubMed  Google Scholar 

  25. Friedman LK, Pellegrini-Giampietro DE, Sperber EF et al (1994) Kainate-induced status epilepticus alters glutamate and GABAA receptor gene expression in adult rat hippocampus: an in situ hybridization study [J]. J Neurosci 14(5 Pt 1):2697–2707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Melo IS, Santos YMO, Costa MA et al (2016) Inhibition of sodium glucose cotransporters following status epilepticus induced by intrahippocampal pilocarpine affects neurodegeneration process in hippocampus [J]. Epilepsy Behav 61:258–268

    Article  PubMed  Google Scholar 

  27. Furtado MDA, Braga GK, Oliveira JAC et al (2002) Behavioral, morphologic, and electroencephalographic evaluation of seizures induced by intrahippocampal microinjection of pilocarpine [J]. Epilepsia 43(Suppl 5):37–39

    Article  CAS  Google Scholar 

  28. Cavarsan CF, Malheiros J, Hamani C et al (2018) Is mossy fiber sprouting a potential therapeutic target for epilepsy? [J]. Front Neurol 9:1023

    Article  PubMed  PubMed Central  Google Scholar 

  29. Morin-Brureau M, Milior G, Royer J et al (2018) Microglial phenotypes in the human epileptic temporal lobe [J]. Brain 141(12):3343–3360

    Article  PubMed  Google Scholar 

  30. Shu Y, Xiao B, Wu Q et al (2016) The ephrin-A5/EphA4 interaction modulates neurogenesis and angiogenesis by the p-Akt and p-ERK pathways in a mouse model of TLE [J]. Mol Neurobiol 53(1):561–576

    Article  CAS  PubMed  Google Scholar 

  31. Leibowitz JA, Natarajan G, Zhou J et al (2019) Sustained somatostatin gene expression reverses kindling-induced increases in the number of dividing type-1 neural stem cells in the hippocampi of behaviorally responsive rats [J]. Epilepsy Res 150:78–94

    Article  CAS  PubMed  Google Scholar 

  32. Lorigados Pedre L, Orozco Suárez S, Morales Chacón L et al (2008) Neuronal death in the neocortex of drug resistant temporal lobe epilepsy patients] [J. Neurologia 23(9):555–65

    CAS  PubMed  Google Scholar 

  33. Zhu X, Liu J, Huang S et al (2019) Neuroprotective effects of isoliquiritigenin against cognitive impairment via suppression of synaptic dysfunction, neuronal injury, and neuroinflammation in rats with kainic acid-induced seizures [J]. Int Immunopharmacol 72:358–366

    Article  CAS  PubMed  Google Scholar 

  34. Cobley JN, Fiorello ML, Bailey DM (2018) 13 reasons why the brain is susceptible to oxidative stress [J]. Redox Biol 15:490–503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Mariani E, Polidori MC, Cherubini A et al (2005) Oxidative stress in brain aging, neurodegenerative and vascular diseases: an overview [J]. J Chromatogr B Analyt Technol Biomed Life Sci 827(1):65–75

    Article  CAS  PubMed  Google Scholar 

  36. Puttachary S, Sharma S, Stark S et al (2015) Seizure-induced oxidative stress in temporal lobe epilepsy [J]. Biomed Res Int 2015:745613

    Article  PubMed  PubMed Central  Google Scholar 

  37. Arican N, Kaya M, Kalayci R et al (2006) Effects of lipopolysaccharide on blood-brain barrier permeability during pentylenetetrazole-induced epileptic seizures in rats [J]. Life Sci 79(1):1–7

    Article  CAS  PubMed  Google Scholar 

  38. Patel M, Liang LP, Roberts LJ (2001) Enhanced hippocampal F2-isoprostane formation following kainate-induced seizures [J]. J Neurochem 79(5):1065–1069

    Article  CAS  PubMed  Google Scholar 

  39. Ambrogini P, Minelli A, Galati C et al (2014) Post-seizure α-tocopherol treatment decreases neuroinflammation and neuronal degeneration induced by status epilepticus in rat hippocampus [J]. Mol Neurobiol 50(1):246–256

    Article  CAS  PubMed  Google Scholar 

  40. Ambrogini P, Albertini MC, Betti M et al (2018) Neurobiological correlates of alpha-tocopherol antiepileptogenic effects and microRNA expression modulation in a rat model of kainate-induced seizures [J]. Mol Neurobiol 55(10):7822–7838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Barichello T, Bonatto F, Agostinho FR et al (2004) Structure-related oxidative damage in rat brain after acute and chronic electroshock [J]. Neurochem Res 29(9):1749–1753

    Article  CAS  PubMed  Google Scholar 

  42. Zupan G, Pilipović K, Hrelja A et al (2008) Oxidative stress parameters in different rat brain structures after electroconvulsive shock-induced seizures [J]. Prog Neuropsychopharmacol Biol Psychiatry 32(3):771–777

    Article  CAS  PubMed  Google Scholar 

  43. Patel M (2004) Mitochondrial dysfunction and oxidative stress: cause and consequence of epileptic seizures [J]. Free Radic Biol Med 37(12):1951–1962

    Article  CAS  PubMed  Google Scholar 

  44. Lin Y, Han Y, Xu J et al (2010) Mitochondrial DNA damage and the involvement of antioxidant defense and repair system in hippocampi of rats with chronic seizures [J]. Cell Mol Neurobiol 30(6):947–954

    Article  CAS  PubMed  Google Scholar 

  45. Liang L-P, Waldbaum S, Rowley S et al (2012) Mitochondrial oxidative stress and epilepsy in SOD2 deficient mice: attenuation by a lipophilic metalloporphyrin [J]. Neurobiol Dis 45(3):1068–76

    Article  CAS  PubMed  Google Scholar 

  46. Liang L-P, Patel M (2004) Mitochondrial oxidative stress and increased seizure susceptibility in Sod2(-/+) mice [J]. Free Radic Biol Med 36(5): 542–54

  47. Liang LP, Ho YS, Patel M (2000) Mitochondrial superoxide production in kainate-induced hippocampal damage [J]. Neuroscience 101(3):563–570

    Article  CAS  PubMed  Google Scholar 

  48. Shin E-J, Ko KH, Kim W-K et al (2008) Role of glutathione peroxidase in the ontogeny of hippocampal oxidative stress and kainate seizure sensitivity in the genetically epilepsy-prone rats [J]. Neurochem Int 52(6):1134–47

    Article  CAS  PubMed  Google Scholar 

  49. Kalita J, Misra UK, Singh LS et al (2019) Oxidative stress in status epilepticus: a clinical-radiological correlation [J]. Brain Res 1704:85–93

    Article  CAS  PubMed  Google Scholar 

  50. Terrone G, Frigerio F, Balosso S et al (2019) Inflammation and reactive oxygen species in status epilepticus: biomarkers and implications for therapy [J]. Epilepsy Behav 101(Pt B):106275

    Article  PubMed  Google Scholar 

  51. Lorigados Pedre L, Gallardo JM, Morales Chacón LM et al (2018) Oxidative stress in patients with drug resistant partial complex seizure [J]. Behavioral sciences (Basel, Switzerland), 8(6)

  52. López J, González ME, Lorigados L et al (2007) Oxidative stress markers in surgically treated patients with refractory epilepsy [J]. Clin Biochem 40(5–6):292–8

    Article  PubMed  Google Scholar 

  53. Lehtinen MK, Tegelberg S, Schipper H et al (2009) Cystatin B deficiency sensitizes neurons to oxidative stress in progressive myoclonus epilepsy, EPM1 [J]. J Neurosci 29(18):5910–5915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Villalpando-Rodriguez GE, Gibson SB (2021) Reactive oxygen species (ROS) regulates different types of cell death by acting as a rheostat [J]. Oxid Med Cell Longev 2021:9912436

  55. Malinska D, Kulawiak B, Kudin AP et al (2010) Complex III-dependent superoxide production of brain mitochondria contributes to seizure-related ROS formation [J]. Biochim Biophys Acta 1797(6–7):1163–1170

    Article  CAS  PubMed  Google Scholar 

  56. Kovac S, Domijan A-M, Walker MC et al (2012) Prolonged seizure activity impairs mitochondrial bioenergetics and induces cell death [J]. J Cell Sci 125(Pt 7):1796–806

  57. Kovac S, Domijan AM, Walker MC et al (2014) Seizure activity results in calcium- and mitochondria-independent ROS production via NADPH and xanthine oxidase activation [J]. Cell Death Dis 5(10):e1442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Pearson-Smith JN, Patel M (2017) Metabolic dysfunction and oxidative stress in epilepsy [J]. Int J Mol Sci, 18(11)

  59. Volmering E, Niehusmann P, Peeva V et al (2016) Neuropathological signs of inflammation correlate with mitochondrial DNA deletions in mesial temporal lobe epilepsy [J]. Acta Neuropathol 132(2):277–288

    Article  CAS  PubMed  Google Scholar 

  60. Zhu X, Shen K, Bai Y et al (2016) NADPH oxidase activation is required for pentylenetetrazole kindling-induced hippocampal autophagy [J]. Free Radic Biol Med 94:230–242

    Article  CAS  PubMed  Google Scholar 

  61. di Maio R, Mastroberardino PG, Hu X et al (2011) Pilocapine alters NMDA receptor expression and function in hippocampal neurons: NADPH oxidase and ERK1/2 mechanisms [J]. Neurobiol Dis 42(3):482–495

    Article  PubMed  Google Scholar 

  62. Shekh-Ahmad T, Lieb A, Kovac S et al (2019) Combination antioxidant therapy prevents epileptogenesis and modifies chronic epilepsy [J]. Redox Biol 26:101278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Lee SH, Choi BY, Kho AR et al (2018) Inhibition of NADPH oxidase activation by Apocynin rescues seizure-induced reduction of adult hippocampal neurogenesis [J]. Int J Mol Sci 19(10)

  64. Pecorelli A, Natrella F, Belmonte G et al (2015) NADPH oxidase activation and 4-hydroxy-2-nonenal/aquaporin-4 adducts as possible new players in oxidative neuronal damage presents in drug-resistant epilepsy [J]. Biochim Biophys Acta 1852(3):507–519

    Article  CAS  PubMed  Google Scholar 

  65. Tsai C-Y, Chan JYH, Hsu K-S et al (2012) Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus [J]. PLoS One 7(3):e33527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kim J-E, Ryu HJ, Kang T-C (2013) Status epilepticus induces vasogenic edema via tumor necrosis factor-α/ endothelin-1-mediated two different pathways [J]. PLoS One 8(9):e74458

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Bishnoi M, Patil CS, Kumar A et al (2007) Co-administration of acetyl-11-keto-beta-boswellic acid, a specific 5-lipoxygenase inhibitor, potentiates the protective effect of COX-2 inhibitors in kainic acid-induced neurotoxicity in mice [J]. Pharmacology 79(1):34–41

    Article  CAS  PubMed  Google Scholar 

  68. Dhir A (2019) An update of cyclooxygenase (COX)-inhibitors in epilepsy disorders [J]. Expert Opin Investig Drugs 28(2):191–205

    Article  CAS  PubMed  Google Scholar 

  69. van Opdenbosch N, Lamkanfi M (2019) Caspases in cell death, inflammation, and disease [J]. Immunity 50(6):1352–1364

    Article  PubMed  PubMed Central  Google Scholar 

  70. Laubach V, Kaufmann R, Bernd A et al (2019) Extrinsic or intrinsic apoptosis by curcumin and light: still a mystery [J]. Int J Mol Sci 20(4)

  71. Kalkavan H, Green DR (2018) MOMP, cell suicide as a BCL-2 family business [J]. Cell Death Differ 25(1):46–55

    Article  CAS  PubMed  Google Scholar 

  72. Li P, Nijhawan D, Budihardjo I et al (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade [J]. Cell 91(4):479–489

    Article  CAS  PubMed  Google Scholar 

  73. Cao X, Wen P, Fu Y et al (2019) Radiation induces apoptosis primarily through the intrinsic pathway in mammalian cells [J]. Cell Signal 62:109337

    Article  CAS  PubMed  Google Scholar 

  74. Zhang X, Cui S-S, Wallace AE et al (2002) Relations between brain pathology and temporal lobe epilepsy [J]. J Neurosci 22(14):6052–61

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Zhen J, Qu Z, Fang H et al (2014) Effects of grape seed proanthocyanidin extract on pentylenetetrazole-induced kindling and associated cognitive impairment in rats [J]. Int J Mol Med 34(2):391–398

  76. Zhang SH, Liu D, Hu Q et al (2019) Ferulic acid ameliorates pentylenetetrazol-induced seizures by reducing neuron cell death [J]. Epilepsy Res 156:106183

    Article  CAS  PubMed  Google Scholar 

  77. Wang A, Si Z, Xue P et al (2019) Tacrolimus protects hippocampal neurons of rats with status epilepticus through suppressing oxidative stress and inhibiting mitochondrial pathway of apoptosis [J]. Brain Res 1715:176–181

    Article  CAS  PubMed  Google Scholar 

  78. Taskiran AS, Ergul M, Gunes H et al (2021) The effects of proton pump inhibitors (pantoprazole) on pentylenetetrazole-induced epileptic seizures in rats and neurotoxicity in the SH-SY5Y human neuroblastoma cell line [J]. Cell Mol Neurobiol 41(1):173–183

    Article  CAS  PubMed  Google Scholar 

  79. Taskiran AS, Ergul M (2021) The modulator action of thiamine against pentylenetetrazole-induced seizures, apoptosis, nitric oxide, and oxidative stress in rats and SH-SY5Y neuronal cell line [J]. Chem Biol Interact 340:109447

    Article  CAS  PubMed  Google Scholar 

  80. Hussein AM, Eldosoky M, El-Shafey M et al (2019) Effects of metformin on apoptosis and α-synuclein in a rat model of pentylenetetrazole-induced epilepsy [J]. Can J Physiol Pharmacol 97(1):37–46

    Article  CAS  PubMed  Google Scholar 

  81. Hasanvand A, Hosseinzadeh A, Saeedavi M et al (2022) Neuroprotective effects of tannic acid against kainic acid-induced seizures in mice [J]. Hum Exp Toxicol 41:9603271221093988

    Article  PubMed  Google Scholar 

  82. Deshpande LS, Lou JK, Mian A et al (2008) Time course and mechanism of hippocampal neuronal death in an in vitro model of status epilepticus: role of NMDA receptor activation and NMDA dependent calcium entry [J]. Eur J Pharmacol 583(1):73–83

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. di Maio R, Mastroberardino PG, Hu X et al (2013) Thiol oxidation and altered NR2B/NMDA receptor functions in in vitro and in vivo pilocarpine models: implications for epileptogenesis [J]. Neurobiol Dis 49:87–98

    Article  PubMed  Google Scholar 

  84. Borowicz-Reutt KK, Czuczwar SJ (2020) Role of oxidative stress in epileptogenesis and potential implications for therapy [J]. Pharmacol Rep 72(5):1218–1226

    Article  PubMed  PubMed Central  Google Scholar 

  85. Mao XY, Zhou HH, Li X et al (2016) Huperzine A alleviates oxidative glutamate toxicity in hippocampal HT22 cells via activating BDNF/TrkB-dependent PI3K/Akt/mTOR signaling pathway [J]. Cell Mol Neurobiol 36(6):915–925

    Article  CAS  PubMed  Google Scholar 

  86. Li Q, Li Q-Q, Jia J-N et al (2018) Sodium valproate ameliorates neuronal apoptosis in a kainic acid model of epilepsy via enhancing PKC-dependent GABAR γ2 serine 327 phosphorylation [J]. Neurochem Res 43(12):2343–52

    Article  CAS  PubMed  Google Scholar 

  87. Beltrán González AN, López Pazos MI, Calvo DJ (2020) Reactive oxygen species in the regulation of the GABA mediated inhibitory neurotransmission [J]. Neuroscience 439:137–45

    Article  PubMed  Google Scholar 

  88. Penna A, Wang D-S, Yu J et al (2014) Hydrogen peroxide increases GABAA receptor-mediated tonic current in hippocampal neurons [J]. J Neurosci 34(32):10624–34

    Article  PubMed  PubMed Central  Google Scholar 

  89. Brookes PS, Yoon Y, Robotham JL et al (2004) Calcium, ATP, and ROS: a mitochondrial love-hate triangle [J]. Am J Physiol Cell Physiol 287(4):C817–C833

    Article  CAS  PubMed  Google Scholar 

  90. Fricker M, Tolkovsky AM, Borutaite V et al (2018) Neuronal cell death [J]. Physiol Rev 98(2):813–880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Harrison JF, Hollensworth SB, Spitz DR et al (2005) Oxidative stress-induced apoptosis in neurons correlates with mitochondrial DNA base excision repair pathway imbalance [J]. Nucleic Acids Res 33(14):4660–4671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Jarrett SG, Liang L-P, Hellier JL et al (2008) Mitochondrial DNA damage and impaired base excision repair during epileptogenesis [J]. Neurobiol Dis 30(1):130–8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Mazzuferi M, Kumar G, van Eyll J et al (2013) Nrf2 defense pathway: experimental evidence for its protective role in epilepsy [J]. Ann Neurol 74(4):560–568

    Article  CAS  PubMed  Google Scholar 

  94. Cao H, Zhang L, Qu Z et al (2021) The protective effect of hydroxylated fullerene pretreatment on pilocarpine-induced status epilepticus [J]. Brain Res 1764:147468

    Article  CAS  PubMed  Google Scholar 

  95. Singh N, Saha L, Kumari P et al (2019) Effect of dimethyl fumarate on neuroinflammation and apoptosis in pentylenetetrazol kindling model in rats [J]. Brain Res Bull 144:233–245

    Article  CAS  PubMed  Google Scholar 

  96. Alyami NM, Abdi S, Alyami HM et al (2022) Proanthocyanidins alleviate pentylenetetrazole-induced epileptic seizures in mice via the antioxidant activity [J]. Neurochem Res

  97. Zhang Y, Zhao J, Afzal O et al (2021) Neuroprotective role of chrysin-loaded poly(lactic-co-glycolic acid) nanoparticle against kindling-induced epilepsy through Nrf2/ARE/HO-1 pathway [J]. J Biochem Mol Toxicol 35(2):e22634

    Article  CAS  PubMed  Google Scholar 

  98. Li D, Bai X, Jiang Y et al (2021) Butyrate alleviates PTZ-induced mitochondrial dysfunction, oxidative stress and neuron apoptosis in mice via Keap1/Nrf2/HO-1 pathway [J]. Brain Res Bull 168:25–35

    Article  CAS  PubMed  Google Scholar 

  99. Yuan X, Fu Z, Ji P et al (2020) Selenium nanoparticles pre-treatment reverse behavioral, oxidative damage, neuronal loss and neurochemical alterations in pentylenetetrazole-induced epileptic seizures in mice [J]. Int J Nanomed 15:6339–6353

    Article  CAS  Google Scholar 

  100. Prakash C, Mishra M, Kumar P et al (2019) Dehydroepiandrosterone alleviates oxidative stress and apoptosis in iron-induced epilepsy via activation of Nrf2/ARE signal pathway [J]. Brain Res Bull 153:181–190

    Article  CAS  PubMed  Google Scholar 

  101. Hayden MS, Ghosh S (2008) Shared principles in NF-kappaB signaling [J]. Cell 132(3):344–362

    Article  CAS  PubMed  Google Scholar 

  102. Zhang Q, Lenardo MJ, Baltimore D (2017) 30 years of NF-κB: a blossoming of relevance to human pathobiology [J]. Cell 168(1–2):37–57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Angkeow P, Deshpande SS, Qi B et al (2002) Redox factor-1: an extra-nuclear role in the regulation of endothelial oxidative stress and apoptosis [J]. Cell Death Differ 9(7):717–725

    Article  CAS  PubMed  Google Scholar 

  104. Guan Z, Basi D, Li Q et al (2005) Loss of redox factor 1 decreases NF-kappaB activity and increases susceptibility of endothelial cells to apoptosis [J]. Arterioscler Thromb Vasc Biol, 25(1)

  105. El Assar M, Angulo J, Rodríguez-Mañas L (2013) Oxidative stress and vascular inflammation in aging [J]. Free Radic Biol Med 65:380–401

    Article  PubMed  Google Scholar 

  106. Singh S, Singh TG (2020) Role of nuclear factor kappa B (NF-κB) signalling in neurodegenerative diseases: an mechanistic approach [J]. Curr Neuropharmacol 18(10):918–935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Cai M, Lin W (2022) The function of NF-kappa B during epilepsy, a potential therapeutic target [J]. Front Neurosci 16:851394

    Article  PubMed  PubMed Central  Google Scholar 

  108. Chuang Y-C, Chen S-D, Lin T-K et al (2010) Transcriptional upregulation of nitric oxide synthase II by nuclear factor-kappaB promotes apoptotic neuronal cell death in the hippocampus following experimental status epilepticus [J]. J Neurosci Res 88(9):1898–907

    CAS  PubMed  Google Scholar 

  109. Maroso M, Balosso S, Ravizza T et al (2010) Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures [J]. Nat Med 16(4):413–419

    Article  CAS  PubMed  Google Scholar 

  110. Arena A, Zimmer TS, van Scheppingen J et al (2019) Oxidative stress and inflammation in a spectrum of epileptogenic cortical malformations: molecular insights into their interdependence [J]. Brain Pathol 29(3):351–365

    Article  CAS  PubMed  Google Scholar 

  111. el Nashar EM, Obydah W, Alghamdi MA et al (2022) Effects of Stevia rebaudiana Bertoni extracts in the rat model of epilepsy induced by pentylenetetrazol: Sirt-1, at the crossroads between inflammation and apoptosis [J]. J Integr Neurosci 21(1):21

    Article  PubMed  Google Scholar 

  112. Rashid S, Wali AF, Rashid SM et al (2021) Zingerone targets status epilepticus by blocking hippocampal neurodegeneration via regulation of redox imbalance, Inflammation and apoptosis [J]. Pharmaceuticals (Basel, Switzerland) 14(2)

  113. Dang J, Paudel YN, Yang X et al (2021) Schaftoside suppresses pentylenetetrazol-induced seizures in zebrafish via suppressing apoptosis, modulating inflammation, and oxidative stress [J]. ACS Chem Neurosci 12(13):2542–2552

    Article  CAS  PubMed  Google Scholar 

  114. Ali AE, Mahdy HM, Elsherbiny DM et al (2018) Rifampicin ameliorates lithium-pilocarpine-induced seizures, consequent hippocampal damage and memory deficit in rats: impact on oxidative, inflammatory and apoptotic machineries [J]. Biochem Pharmacol 156:431–443

    Article  CAS  PubMed  Google Scholar 

  115. Al Omairi NE, Albrakati A, Alsharif KF et al (2022) Selenium nanoparticles with prodigiosin rescue hippocampal damage associated with epileptic seizures induced by pentylenetetrazole in rats [J]. Biology 11(3)

  116. Sedaghat R, Taab Y, Kiasalari Z et al (2017) Berberine ameliorates intrahippocampal kainate-induced status epilepticus and consequent epileptogenic process in the rat: underlying mechanisms [J]. Biomed Pharmacother 87:200–208

    Article  CAS  PubMed  Google Scholar 

  117. Deng X, Wang M, Hu S et al (2019) The neuroprotective effect of astaxanthin on pilocarpine-induced status epilepticus in rats [J]. Front Cell Neurosci 13:123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Son Y, Cheong Y-K, Kim N-H et al (2011) Mitogen-activated protein kinases and reactive oxygen species: how can ros activate MAPK pathways? [J]. J Signal Transduct 2011:792639

    Article  PubMed  PubMed Central  Google Scholar 

  119. Huang R, Zhu Y, Lin L et al (2020) Solid lipid nanoparticles enhanced the neuroprotective role of curcumin against epilepsy through activation of Bcl-2 family and P38 MAPK pathways [J]. ACS Chem Neurosci 11(13):1985–1995

    Article  CAS  PubMed  Google Scholar 

  120. Sun X, Kong L, Zhou L (2018) Protective effect of Fructus corni polysaccharide on hippocampal tissues and its relevant mechanism in epileptic rats induced by lithium chloride-pilocarpine [J]. Exp Ther Med 16(1):445–451

    PubMed  PubMed Central  Google Scholar 

  121. Yang X, Zhang H, Wu J et al (2018) Humanin attenuates NMDA-induced excitotoxicity by inhibiting ROS-dependent JNK/p38 MAPK pathway [J]. Int J Mol Sci 19(10)

  122. de Lemos L, Junyent F, Camins A et al (2018) Neuroprotective effects of the absence of JNK1 or JNK3 isoforms on kainic acid-induced temporal lobe epilepsy-like symptoms [J]. Mol Neurobiol 55(5):4437–4452

    PubMed  Google Scholar 

  123. Castro-Torres RD, Landa J, Rabaza M et al (2019) JNK Isoforms are involved in the control of adult hippocampal neurogenesis in mice, both in physiological conditions and in an experimental model of temporal lobe epilepsy [J]. Mol Neurobiol 56(8):5856–5865

    Article  CAS  PubMed  Google Scholar 

  124. de Lemos L, Junyent F, Verdaguer E et al (2010) Differences in activation of ERK1/2 and p38 kinase in Jnk3 null mice following KA treatment [J]. J Neurochem 114(5):1315–1322

    PubMed  Google Scholar 

  125. Guo Y, Cai Y, Zhang X (2020) Icariin ameliorates the cognitive function in an epilepsy neonatal rat model by blocking the GluR2/ERK I/II pathway [J]. Folia Neuropathol 58(3):245–252

    Article  PubMed  Google Scholar 

  126. Ho KK, Myatt SS, Lam EWF (2008) Many forks in the path: cycling with FoxO [J]. Oncogene 27(16):2300–2311

    Article  CAS  PubMed  Google Scholar 

  127. Hagenbuchner J, Kuznetsov A, Hermann M et al (2012) FOXO3-induced reactive oxygen species are regulated by BCL2L11 (Bim) and SESN3 [J]. J Cell Sci 125(Pt 5):1191–1203

    Article  CAS  PubMed  Google Scholar 

  128. Wu H, Meng Q, Zhang Y et al (2021) Upregulated Nmnat2 causes neuronal death and increases seizure susceptibility in temporal lobe epilepsy [J]. Brain Res Bull 167:1–10

    Article  CAS  PubMed  Google Scholar 

  129. Kim YS, Choi MY, Lee DH et al (2014) Decreased interaction between FoxO3a and Akt correlates with seizure-induced neuronal death [J]. Epilepsy Res 108(3):367–378

    Article  CAS  PubMed  Google Scholar 

  130. Caballero-Caballero A, Engel T, Martinez-Villarreal J et al (2013) Mitochondrial localization of the forkhead box class O transcription factor FOXO3a in brain [J]. J Neurochem 124(6):749–756

    Article  CAS  PubMed  Google Scholar 

  131. Dhuriya YK, Sharma D (2018) Necroptosis: a regulated inflammatory mode of cell death [J]. J Neuroinflammation 15(1):199

    Article  PubMed  PubMed Central  Google Scholar 

  132. Conrad M, Angeli JPF, Vandenabeele P et al (2016) Regulated necrosis: disease relevance and therapeutic opportunities [J]. Nat Rev Drug Discovery 15(5):348–366

    Article  CAS  PubMed  Google Scholar 

  133. Zhao J, Jitkaew S, Cai Z et al (2012) Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis [J]. Proc Natl Acad Sci U S A 109(14):5322–5327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Mármol I, Virumbrales-Muñoz M, Quero J et al (2017) Alkynyl gold(I) complex triggers necroptosis via ROS generation in colorectal carcinoma cells [J]. J Inorg Biochem 176:123–33

    Article  PubMed  Google Scholar 

  135. Zhao L, Lin H, Chen S et al (2018) Hydrogen peroxide induces programmed necrosis in rat nucleus pulposus cells through the RIP1/RIP3-PARP-AIF pathway [J]. J Orthop Res 36(4):1269–1282

  136. Han CH, Guan ZB, Zhang PX et al (2018) Oxidative stress induced necroptosis activation is involved in the pathogenesis of hyperoxic acute lung injury [J]. Biochem Biophys Res Commun 495(3):2178–2183

    Article  CAS  PubMed  Google Scholar 

  137. Ye Y-C, Wang H-J, Yu L et al (2012) RIP1-mediated mitochondrial dysfunction and ROS production contributed to tumor necrosis factor alpha-induced L929 cell necroptosis and autophagy [J]. Int Immunopharmacol 14(4): 674–82

  138. Yang Z, Wang Y, Zhang Y et al (2018) RIP3 targets pyruvate dehydrogenase complex to increase aerobic respiration in TNF-induced necroptosis [J]. Nat Cell Biol 20(2):186–197

    Article  CAS  PubMed  Google Scholar 

  139. Shindo R, Kakehashi H, Okumura K et al (2013) Critical contribution of oxidative stress to TNFα-induced necroptosis downstream of RIPK1 activation [J]. Biochem Biophys Res Commun 436(2):212–216

    Article  CAS  PubMed  Google Scholar 

  140. Schenk B, Fulda S (2015) Reactive oxygen species regulate Smac mimetic/TNFα-induced necroptotic signaling and cell death [J]. Oncogene 34(47):5796–5806

    Article  CAS  PubMed  Google Scholar 

  141. Cai Q, Gan J, Luo R et al (2017) The role of necroptosis in status epilepticus-induced brain injury in juvenile rats [J]. Epilepsy Behav 75:134–142

    Article  PubMed  Google Scholar 

  142. Lin D-Q, Cai X-Y, Wang C-H et al (2020) Optimal concentration of necrostatin-1 for protecting against hippocampal neuronal damage in mice with status epilepticus [J]. Neural Regen Res 15(5):936–43

    Article  PubMed  Google Scholar 

  143. Ohsawa I, Ishikawa M, Takahashi K et al (2007) Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals [J]. Nat Med 13(6):688–694

    Article  CAS  PubMed  Google Scholar 

  144. Jia R, Jia N, Yang F et al (2019) Hydrogen alleviates necroptosis and cognitive deficits in lithium-pilocarpine model of status epilepticus [J]. Cell Mol Neurobiol 39(6):857–869

    Article  CAS  PubMed  Google Scholar 

  145. Wang J, Liu Y, Li XH et al (2017) Curcumin protects neuronal cells against status-epilepticus-induced hippocampal damage through induction of autophagy and inhibition of necroptosis [J]. Can J Physiol Pharmacol 95(5):501–509

    Article  CAS  PubMed  Google Scholar 

  146. Wang J, Li Y, Huang WH et al (2017) The protective effect of aucubin from Eucommia ulmoides against status epilepticus by inducing autophagy and inhibiting necroptosis [J]. Am J Chin Med 45(3):557–573

    Article  CAS  PubMed  Google Scholar 

  147. Nakatogawa H, Suzuki K, Kamada Y et al (2009) Dynamics and diversity in autophagy mechanisms: lessons from yeast [J]. Nat Rev Mol Cell Biol 10(7):458–467

    Article  CAS  PubMed  Google Scholar 

  148. Giorgi FS, Biagioni F, Lenzi P et al (2015) The role of autophagy in epileptogenesis and in epilepsy-induced neuronal alterations [J]. J Neural Transm (Vienna, Austria : 1996) 122(6): 849–62

  149. Xie R, Li T, Qiao X et al (2021) The protective role of E-64d in hippocampal excitotoxic neuronal injury induced by glutamate in HT22 hippocampal neuronal cells [J]. Neural Plast 2021:7174287

    Article  PubMed  PubMed Central  Google Scholar 

  150. Cao LR, 2016 #5988}, Chen R, Xu J et al (2009) Vitamin E inhibits activated chaperone-mediated autophagy in rats with status epilepticus [J]. Neuroscience 161(1):73–7.

  151. Ornatowski W, Lu Q, Yegambaram M et al (2020) Complex interplay between autophagy and oxidative stress in the development of pulmonary disease [J]. Redox Biol 36:101679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Yun HR, Jo YH, Kim J et al (2020) Roles of autophagy in oxidative stress [J]. Int J Mol Sci 21(9)

  153. Li L, Tan J, Miao Y et al (2015) ROS and autophagy: interactions and molecular regulatory mechanisms [J]. Cell Mol Neurobiol 35(5):615–621

    Article  PubMed  Google Scholar 

  154. Lee J, Giordano S, Zhang J (2012) Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling [J]. Biochem J 441(2):523–540

    Article  CAS  PubMed  Google Scholar 

  155. Pickles S, Vigié P, Youle RJ (2018) Mitophagy and quality control mechanisms in mitochondrial maintenance [J]. Curr Biol CB 28(4):R170-R85

  156. McMahon J, Huang X, Yang J et al (2012) Impaired autophagy in neurons after disinhibition of mammalian target of rapamycin and its contribution to epileptogenesis [J]. J Neurosci 32(45):15704–15714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Zhang YX, Qiao S, Cai MT et al (2021) Association between autophagy-related protein 5 gene polymorphisms and epilepsy in Chinese patients [J]. Neurosci Lett 753:135870

    Article  CAS  PubMed  Google Scholar 

  158. Carvill GL, Liu A, Mandelstam S et al (2018) Severe infantile onset developmental and epileptic encephalopathy caused by mutations in autophagy gene WDR45 [J]. Epilepsia 59(1):e5–e13

    Article  CAS  PubMed  Google Scholar 

  159. Gao D, Ma L, Xie Y et al (2022) Electroacupuncture promotes autophagy by regulating the AKT/mTOR signaling pathway in temporal lobe epilepsy [J]. Neurochem Res

  160. Zhu W, Zhu J, Zhao S et al (2020) Xenon exerts neuroprotective effects on kainic acid-induced acute generalized seizures in rats via increased autophagy [J]. Front Cell Neurosci 14:582872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Du TT, Zhu G, Chen Y et al (2020) Anterior thalamic nucleus stimulation protects hippocampal neurons by activating autophagy in epileptic monkeys [J]. Aging (Albany NY) 12(7):6324–6339

    Article  CAS  Google Scholar 

  162. Ali SO, Shahin NN, Safar MM et al (2019) Therapeutic potential of endothelial progenitor cells in a rat model of epilepsy: role of autophagy [J]. J Adv Res 18:101–112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Wang BH, Hou Q, Lu YQ et al (2018) Ketogenic diet attenuates neuronal injury via autophagy and mitochondrial pathways in pentylenetetrazol-kindled seizures [J]. Brain Res 1678:106–115

    Article  CAS  PubMed  Google Scholar 

  164. Nader MA, Ateyya H, El-Shafey M et al (2018) Sitagliptin enhances the neuroprotective effect of pregabalin against pentylenetetrazole-induced acute epileptogenesis in mice: Implication of oxidative, inflammatory, apoptotic and autophagy pathways [J]. Neurochem Int 115:11–23

    Article  CAS  PubMed  Google Scholar 

  165. Li Q, Han Y, Du J et al (2018) Recombinant human erythropoietin protects against brain injury through blunting the mTORC1 pathway in the developing brains of rats with seizures [J]. Life Sci 194:15–25

    Article  CAS  PubMed  Google Scholar 

  166. Hosseinzadeh M, Nikseresht S, Khodagholi F et al (2016) Cannabidiol post-treatment alleviates rat epileptic-related behaviors and activates hippocampal cell autophagy pathway along with antioxidant defense in chronic phase of pilocarpine-induced seizure [J]. J Mol Neurosci: MN 58(4):432–440

    Article  CAS  PubMed  Google Scholar 

  167. Wu M, Liu X, Chi X et al (2018) Mitophagy in refractory temporal lobe epilepsy patients with hippocampal sclerosis [J]. Cell Mol Neurobiol 38(2):479–486

    Article  CAS  PubMed  Google Scholar 

  168. Xiao D, LV J, Zheng Z et al (2021) Mechanisms of microRNA‑142 in mitochondrial autophagy and hippocampal damage in a rat model of epilepsy [J]. Int J Mol Med 47(6)

  169. Wu G, Liu J, Li S et al (2020) Glycyrrhizic acid protects juvenile epileptic rats against hippocampal damage through activation of Sirtuin3 [J]. Brain Res Bull 164:98–106

    Article  CAS  PubMed  Google Scholar 

  170. Jin MF, Ni H, Li LL (2018) Leptin maintained zinc homeostasis against glutamate-induced excitotoxicity by preventing mitophagy-mediated mitochondrial activation in HT22 hippocampal neuronal cells [J]. Front Neurol 9:322

    Article  PubMed  PubMed Central  Google Scholar 

  171. Cheng Y, Cui Y, Zhai Y et al (2021) Neuroprotective effects of exogenous irisin in kainic acid-induced status epilepticus [J]. Front Cell Neurosci 15:738533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Yu J, Cheng Y, Cui Y et al (2022) Anti-seizure and neuronal protective effects of irisin in kainic acid-induced chronic epilepsy model with spontaneous seizures [J]. Neurosci Bull

  173. Yang P, Qin Y, Zhu Y et al (2020) Chaihu-Longgu-Muli decoction relieves epileptic symptoms by improving autophagy in hippocampal neurons [J]. J Ethnopharmacol 259:112990

    Article  CAS  PubMed  Google Scholar 

  174. Peng Y, Chen L, Qu Y et al (2021) Rosiglitazone prevents autophagy by regulating Nrf2-antioxidant response element in a rat model of lithium-pilocarpine-induced status epilepticus [J]. Neuroscience 455:212–222

    Article  CAS  PubMed  Google Scholar 

  175. Li LL, Li YC, Zhao DJ et al (2018) Leptin-regulated autophagy plays a role in long-term neurobehavioral injury after neonatal seizures and the regulation of zinc/cPLA2 and CaMK II signaling in cerebral cortex [J]. Epilepsy Res 146:103–111

    Article  CAS  PubMed  Google Scholar 

  176. Li LL, Jin MF, Ni H (2018) Zinc/CaMK II Associated-mitophagy signaling contributed to hippocampal mossy fiber sprouting and cognitive deficits following neonatal seizures and its regulation by chronic leptin treatment [J]. Front Neurol 9:802

    Article  PubMed  PubMed Central  Google Scholar 

  177. Hussein AM, Eldosoky M, El-Shafey M et al (2019) Effects of GLP-1 receptor activation on a pentylenetetrazole-kindling rat model [J]. Brain Sci 9(5)

  178. Hussein AM, Adel M, El-Mesery M et al (2018) L-Carnitine modulates epileptic seizures in pentylenetetrazole-kindled rats via suppression of apoptosis and autophagy and upregulation of Hsp70 [J]. Brain Sci 8(3)

  179. Dong Y, Wang S, Zhang T et al (2013) Ascorbic acid ameliorates seizures and brain damage in rats through inhibiting autophagy [J]. Brain Res 1535:115–123

    Article  CAS  PubMed  Google Scholar 

  180. Cao J, Tang C, Gao M et al (2020) Hyperoside alleviates epilepsy-induced neuronal damage by enhancing antioxidant levels and reducing autophagy [J]. J Ethnopharmacol 257:112884

    Article  CAS  PubMed  Google Scholar 

  181. Attia GM, Elmansy RA, Elsaed WM (2019) Neuroprotective effect of nilotinib on pentylenetetrazol-induced epilepsy in adult rat hippocampus: involvement of oxidative stress, autophagy, inflammation, and apoptosis [J]. Folia Neuropathol 57(2):146–160

    Article  PubMed  Google Scholar 

  182. Cookson BT, Brennan MA (2001) Pro-inflammatory programmed cell death [J]. Trends Microbiol 9(3):113–114

    Article  CAS  PubMed  Google Scholar 

  183. Xia X, Wang X, Zheng Y et al (2019) What role does pyroptosis play in microbial infection? [J]. J Cell Physiol 234(6):7885–7892

    Article  CAS  PubMed  Google Scholar 

  184. Rathinam VAK, Fitzgerald KA (2016) Inflammasome complexes: emerging mechanisms and effector functions [J]. Cell 165(4):792–800

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Fang Y, Tian S, Pan Y et al (2020) Pyroptosis: a new frontier in cancer [J]. Biomed Pharmacother 121:109595

    Article  CAS  PubMed  Google Scholar 

  186. Jorgensen I, Miao EA (2015) Pyroptotic cell death defends against intracellular pathogens [J]. Immunol Rev 265(1):130–142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Du K, He M, Zhao D et al (2022) Mechanism of cell death pathways in status epilepticus and related therapeutic agents [J]. Biomed Pharmacother 149:112875

    Article  CAS  PubMed  Google Scholar 

  188. He Y, Hara H, NúñEZ G (2016) Mechanism and regulation of NLRP3 inflammasome activation [J]. Trends Biochem Sci 41(12):1012–1021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Qiu Z, He Y, Ming H et al (2019) Lipopolysaccharide (LPS) aggravates high glucose- and hypoxia/reoxygenation-induced injury through activating ROS-dependent NLRP3 inflammasome-mediated pyroptosis in H9C2 cardiomyocytes [J]. J Diabetes Res 2019:8151836

    Article  PubMed  PubMed Central  Google Scholar 

  190. Mai W, Xu Y, Xu J et al (2020) Berberine inhibits nod-like receptor family pyrin domain containing 3 inflammasome activation and pyroptosis in nonalcoholic steatohepatitis the ROS/TXNIP axis [J]. Front Pharmacol 11:185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Xu T, Sun L, Shen X et al (2019) NADPH oxidase 2-mediated NLRP1 inflammasome activation involves in neuronal senescence in hippocampal neurons in vitro [J]. Int Immunopharmacol 69:60–70

    Article  CAS  PubMed  Google Scholar 

  192. Wang Y, Shi P, Chen Q et al (2019) Mitochondrial ROS promote macrophage pyroptosis by inducing GSDMD oxidation [J]. J Mol Cell Biol 11(12):1069–1082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Evavold CL, Hafner-Bratkovič I, Devant P et al (2021) Control of gasdermin D oligomerization and pyroptosis by the Ragulator-Rag-mTORC1 pathway [J]. Cell 184(17)

  194. de Brito Cristina, Toscano E, Leandro Marciano Vieira É, Boni Rocha Dias B et al (2021) NLRP3 and NLRP1 inflammasomes are up-regulated in patients with mesial temporal lobe epilepsy and may contribute to overexpression of caspase-1 and IL-β in sclerotic hippocampi [J]. Brain Res 1752:147230

    Article  Google Scholar 

  195. Tan CC, Zhang JG, Tan MS et al (2015) NLRP1 inflammasome is activated in patients with medial temporal lobe epilepsy and contributes to neuronal pyroptosis in amygdala kindling-induced rat model [J]. J Neuroinflammation 12:18

    Article  PubMed  PubMed Central  Google Scholar 

  196. Jiang Q, Tang G, Zhong XM et al (2021) Role of Stat3 in NLRP3/caspase-1-mediated hippocampal neuronal pyroptosis in epileptic mice [J]. Synapse (New York, NY) 75(12):e22221

    Article  CAS  Google Scholar 

  197. Wang Z, Zhou L, An D et al (2019) TRPV4-induced inflammatory response is involved in neuronal death in pilocarpine model of temporal lobe epilepsy in mice [J]. Cell Death Dis 10(6):386

    Article  PubMed  PubMed Central  Google Scholar 

  198. Xia S, Yang P, Li F et al (2021) Chaihu-Longgu-Muli Decoction exerts an antiepileptic effect in rats by improving pyroptosis in hippocampal neurons [J]. J Ethnopharmacol 270:113794

    Article  CAS  PubMed  Google Scholar 

  199. Li X, Lin J, Hua Y et al (2021) Agmatine alleviates epileptic seizures and hippocampal neuronal damage by inhibiting gasdermin D-mediated pyroptosis [J]. Front Pharmacol 12:627557

  200. Tashakori-Miyanroudi M, Ramazi S, Hashemi P et al (2022) Acetyl-L-carnitine exerts neuroprotective and anticonvulsant effect in kainate murine model of temporal lobe epilepsy [J]. J Mol Neurosci : MN 72(6):1224–1233

    Article  CAS  PubMed  Google Scholar 

  201. Ramazi S, Fahanik-Babaei J, Mohamadi-Zarch SM et al (2022) Paeonol exerts neuroprotective and anticonvulsant effects in intrahippocampal kainate model of temporal lobe epilepsy [J]. J Chem Neuroanat 102121

  202. Ramazi S, Fahanik-Babaei J, Mohamadi-Zarch SM et al (2020) Neuroprotective and anticonvulsant effects of sinomenine in kainate rat model of temporal lobe epilepsy: involvement of oxidative stress, inflammation and pyroptosis [J]. J Chem Neuroanat 108:101800

    Article  CAS  PubMed  Google Scholar 

  203. Dixon SJ, Lemberg KM, Lamprecht MR et al (2012) Ferroptosis: an iron-dependent form of nonapoptotic cell death [J]. Cell 149(5):1060–1072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Zhu J, Xiong Y, Zhang Y et al (2020) The molecular mechanisms of regulating oxidative stress-induced ferroptosis and therapeutic strategy in tumors [J]. Oxid Med Cell Longev 2020:8810785

    Article  PubMed  PubMed Central  Google Scholar 

  205. Capelletti MM, Manceau H, Puy H et al (2020) Ferroptosis in liver diseases: an overview [J]. Int J Mol Sci 21(14)

  206. Su L-J, Zhang J-H, Gomez H et al (2019) Reactive oxygen species-induced lipid peroxidation in apoptosis, autophagy, and ferroptosis [J]. Oxid Med Cell Longev 2019:5080843

    Article  PubMed  PubMed Central  Google Scholar 

  207. Chen S, Chen Y, Zhang Y et al (2020) Iron metabolism and ferroptosis in epilepsy [J]. Front Neurosci 14:601193

    Article  PubMed  PubMed Central  Google Scholar 

  208. Hou L, Huang R, Sun F et al (2019) NADPH oxidase regulates paraquat and maneb-induced dopaminergic neurodegeneration through ferroptosis [J]. Toxicology 417:64–73

    Article  CAS  PubMed  Google Scholar 

  209. Ye Q, Zeng C, Dong L et al (2019) Inhibition of ferroptosis processes ameliorates cognitive impairment in kainic acid-induced temporal lobe epilepsy in rats [J]. Am J Transl Res 11(2):875–884

    CAS  PubMed  PubMed Central  Google Scholar 

  210. Mao XY, Zhou HH, Jin WL (2019) Ferroptosis induction in pentylenetetrazole kindling and pilocarpine-induced epileptic seizures in mice [J]. Front Neurosci 13:721

    Article  PubMed  PubMed Central  Google Scholar 

  211. Akyuz E, Doganyigit Z, Eroglu E et al (2021) Myocardial iron overload in an experimental model of sudden unexpected death in epilepsy [J]. Front Neurol 12:609236

    Article  PubMed  PubMed Central  Google Scholar 

  212. Petrillo S, Pietrafusa N, Trivisano M et al (2021) Imbalance of systemic redox biomarkers in children with epilepsy: role of ferroptosis [J]. Antioxidants (Basel) 10(8)

  213. Ambrogini P, Betti M, Galati C et al (2016) α-Tocopherol and hippocampal neural plasticity in physiological and pathological conditions [J]. Int J Mol Sci 17(12)

  214. Zhang X, Wu S, Guo C et al (2021) Vitamin E exerts neuroprotective effects in pentylenetetrazole kindling epilepsy via suppression of ferroptosis [J]. Neurochem Res

  215. Lee J-J, Chang-Chien G-P, Lin S et al (2022) 5-Lipoxygenase inhibition protects retinal pigment epithelium from sodium iodate-induced ferroptosis and prevents retinal degeneration [J]. Oxid Med Cell Longev 2022:1792894

    Article  PubMed  PubMed Central  Google Scholar 

  216. Li Q, Li Q-Q, Jia J-N et al (2019) Baicalein exerts neuroprotective effects in FeCl-induced posttraumatic epileptic seizures suppressing ferroptosis [J]. Front Pharmacol 10:638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  217. Liu Y, Wang W, Li Y et al (2015) The 5-lipoxygenase inhibitor zileuton confers neuroprotection against glutamate oxidative damage by inhibiting ferroptosis [J]. Biol Pharm Bull 38(8):1234–1239

    Article  CAS  PubMed  Google Scholar 

  218. Miotto G, Rossetto M, di Paolo ML et al (2020) Insight into the mechanism of ferroptosis inhibition by ferrostatin-1 [J]. Redox Biol 28:101328

    Article  CAS  PubMed  Google Scholar 

  219. Ye Q, Zeng C, Luo C et al (2020) Ferrostatin-1 mitigates cognitive impairment of epileptic rats by inhibiting P38 MAPK activation [J]. Epilepsy Behav 103(Pt A):106670

    Article  PubMed  Google Scholar 

  220. Chen KN, Guan QW, Yin XX et al (2022) Ferrostatin-1 obviates seizures and associated cognitive deficits in ferric chloride-induced posttraumatic epilepsy via suppressing ferroptosis [J]. Free Radic Biol Med 179:109–118

    Article  CAS  PubMed  Google Scholar 

  221. Shao C, Yuan J, Liu Y et al (2020) Epileptic brain fluorescent imaging reveals apigenin can relieve the myeloperoxidase-mediated oxidative stress and inhibit ferroptosis [J]. Proc Natl Acad Sci U S A 117(19):10155–10164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  222. Jia J-N, Yin X-X, Li Q et al (2020) Neuroprotective effects of the anti-cancer drug lapatinib against epileptic seizures via suppressing glutathione peroxidase 4-dependent ferroptosis [J]. Front Pharmacol 11:601572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  223. Shao C, Liu Y, Chen Z et al (2022) 3D two-photon brain imaging reveals dihydroartemisinin exerts antiepileptic effects by modulating iron homeostasis [J]. Cell Chem Biol 29(1):43-56.e12

    Article  CAS  PubMed  Google Scholar 

  224. Deragon MA, McCaig WD, Patel PS et al (2020) Mitochondrial ROS prime the hyperglycemic shift from apoptosis to necroptosis [J]. Cell Death Discov 6(1):132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Xie N, Li Y, Wang C et al (2020) FAM134B attenuates seizure-induced apoptosis and endoplasmic reticulum stress in hippocampal neurons by promoting autophagy [J]. Cell Mol Neurobiol 40(8):1297–1305

    Article  CAS  PubMed  Google Scholar 

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This research was supported by Jilin Scientific and Technological Development Program (grant nos. 2019SCZ044; 20200201364JC).

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  1. Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, 130000 126 Sendai Street, Erdao District, Changchun city, Jilin Province, China

    Haogang Sun, Xinxin Li, Qi Guo & Songyan Liu

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Sun, H., Li, X., Guo, Q. et al. Research progress on oxidative stress regulating different types of neuronal death caused by epileptic seizures. Neurol Sci 43, 6279–6298 (2022). https://doi.org/10.1007/s10072-022-06302-6

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