title: Seizure-induced oxidative stress in temporal lobe epilepsy.
abstract: An insult to the brain (such as the first seizure) causes excitotoxicity, neuroinflammation, and production of reactive oxygen/nitrogen species (ROS/RNS). ROS and RNS produced during status epilepticus (SE) overwhelm the mitochondrial natural antioxidant defense mechanism. This leads to mitochondrial dysfunction and damage to the mitochondrial DNA. This in turn affects synthesis of various enzyme complexes that are involved in electron transport chain. Resultant effects that occur during epileptogenesis include lipid peroxidation, reactive gliosis, hippocampal neurodegeneration, reorganization of neural networks, and hypersynchronicity. These factors predispose the brain to spontaneous recurrent seizures (SRS), which ultimately establish into temporal lobe epilepsy (TLE). This review discusses some of these issues. Though antiepileptic drugs (AEDs) are beneficial to control/suppress seizures, their long term usage has been shown to increase ROS/RNS in animal models and human patients. In established TLE, ROS/RNS are shown to be harmful as they can increase the susceptibility to SRS. Further, in this paper, we review briefly the data from animal models and human TLE patients on the adverse effects of antiepileptic medications and the plausible ameliorating effects of antioxidants as an adjunct therapy.
authors: Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, USA.
authors: Sreekanth
authors: 0000-0002-2508-6803
authors: S
authors: Puttachary
authors: Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, USA.
authors: Shaunik
authors: 0000-0002-3352-6397
authors: S
authors: Sharma
authors: Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, USA.
authors: Sara
authors: 0000-0002-1224-5932
authors: S
authors: Stark
authors: Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, USA.
authors: Thimmasettappa
authors: 0000-0002-9326-1896
authors: T
authors: Thippeswamy
mesh_terms: D000818:Animals; D004833:Epilepsy, Temporal Lobe; D006801:Humans; D018384:Oxidative Stress; D012640:Seizures; D015398:Signal Transduction
references: Drug Metab Rev. 2011 May;43(2):138-51
references: 21428697
references: Ann Neurol. 2005 Jan;57(1):111-8
references: 15622525
references: Neurology. 2005 Jan 25;64(2):326-33
references: 15668432
references: Acta Neuropathol. 2010 Jan;119(1):7-35
references: 20012068
references: Neurosci Lett. 1994 Feb 28;168(1-2):193-6
references: 8028775
references: Neurochem Int. 2004 Jul;45(1):103-16
references: 15082228
references: J Cereb Blood Flow Metab. 2008 Mar;28(3):468-81
references: 17726492
references: PLoS One. 2012;7(2):e30763
references: 22363486
references: Neurology. 2001 Oct 23;57(8):1422-7
references: 11673583
references: J Neurosci. 1996 Apr 15;16(8):2508-21
references: 8786427
references: Biull Eksp Biol Med. 1995 Jul;120(7):20-2
references: 8527771
references: Neurochem Int. 2013 Dec;63(7):635-7
references: 24021493
references: Antioxid Redox Signal. 2009 Mar;11(3):669-702
references: 19014277
references: Brain Res Bull. 1985 Jul;15(1):39-60
references: 2862970
references: J Neuroimmunol. 2010 Jul 27;224(1-2):51-5
references: 20554024
references: Pediatr Neurol. 2007 May;36(5):281-92
references: 17509459
references: Lancet. 2004 Jan 3;363(9402):28-37
references: 14723991
references: Adv Exp Med Biol. 1986;203:631-45
references: 3024464
references: J Cereb Blood Flow Metab. 2004 Sep;24(9):972-85
references: 15356418
references: J Neural Transm Suppl. 2003;(65):101-44
references: 12946052
references: J Integr Med. 2013 Sep;11(5):337-42
references: 24063781
references: Free Radic Biol Med. 2004 Mar 1;36(5):542-54
references: 14980699
references: Brain Res. 2001 Mar 9;894(1):131-40
references: 11245823
references: Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11534-9
references: 11016948
references: Cell. 1990 Jun 15;61(6):931-7
references: 2112427
references: Neurochem Int. 2013 Dec;63(7):670-81
references: 23791709
references: Neurosci Lett. 2014 Apr 17;565:30-8
references: 24406153
references: J Neurochem. 1989 Feb;52(2):381-9
references: 2911023
references: Neurology. 1997 Dec;49(6):1655-61
references: 9409363
references: Nat Neurosci. 2007 Nov;10(11):1387-94
references: 17965659
references: Clin Chim Acta. 2001 Jan;303(1-2):19-24
references: 11163018
references: Br J Pharmacol. 2012 Jan;165(1):20-34
references: 21564084
references: J Neuroinflammation. 2011 May 24;8:57
references: 21609430
references: Brain Res. 1999 Nov 20;847(2):347-51
references: 10575107
references: Neuroscience. 2000;97(3):431-5
references: 10828526
references: J Immunol. 1994 Apr 1;152(7):3578-85
references: 8144936
references: Ann N Y Acad Sci. 2002 Apr;959:238-50
references: 11976199
references: Microsurgery. 2005;25(4):338-45
references: 15880470
references: Neurosci Lett. 2008 Aug 15;441(1):115-9
references: 18583041
references: Nat Rev Neurosci. 2005 Aug;6(8):626-40
references: 16025096
references: Nat Med. 2005 Sep;11(9):973-81
references: 16116433
references: Neuron Glia Biol. 2010 Feb;6(1):11-7
references: 20113536
references: Int J Mol Sci. 2013 Sep 05;14(9):18284-318
references: 24013377
references: Curr Treat Options Neurol. 2008 Nov;10(6):410-9
references: 18990309
references: Arterioscler Thromb Vasc Biol. 2011 May;31(5):986-1000
references: 21508345
references: Acc Chem Res. 2009 Mar 17;42(3):439-51
references: 19154146
references: Neurologist. 2005 Nov;11(6):348-61
references: 16286878
references: Free Radic Biol Med. 2006 Jan 15;40(2):316-22
references: 16413413
references: Methods Enzymol. 2008;441:173-96
references: 18554535
references: J Neurochem. 1990 Dec;55(6):2091-7
references: 1977889
references: FEBS J. 2009 May;276(9):2478-93
references: 19476489
references: Acta Neurol Scand. 2005 May;111(5):291-300
references: 15819708
references: Mol Cell Biochem. 1998 Jan;178(1-2):299-303
references: 9546613
references: Oxid Med Cell Longev. 2012;2012:795259
references: 22848783
references: J Neurol Neurosurg Psychiatry. 2006 Apr;77(4):489-94
references: 16543528
references: J Appl Toxicol. 2001 Sep-Oct;21(5):403-7
references: 11746182
references: Toxicol Lett. 2002 Mar 24;129(1-2):99-105
references: 11879979
references: Exp Neurol. 2008 Feb;209(2):294-301
references: 17617407
references: Free Radic Res. 2002 Nov;36(11):1139-46
references: 12592665
references: Neurobiol Dis. 2008 Jun;30(3):281-292
references: 18375135
references: Neurosci Lett. 2007 Jan 10;411(2):152-7
references: 17092649
references: Int J Biochem Cell Biol. 2007;39(1):44-84
references: 16978905
references: Neurologia. 1996 Dec;11 Suppl 4:29-32
references: 9019099
references: Prog Brain Res. 2001;132:525-32
references: 11545017
references: Can J Neurol Sci. 2000 May;27 Suppl 1:S6-10; discussion S20-1
references: 10830320
references: J Neurosci Res. 2001 Aug 15;65(4):322-31
references: 11494368
references: J Neurosci Res. 2010 Feb 15;88(3):519-29
references: 19774666
references: Epilepsy Res. 2004 Feb;58(2-3):93-105
references: 15120741
references: J Neurosci Res. 1997 Dec 15;50(6):1023-9
references: 9452017
references: Curr Neuropharmacol. 2012 Dec;10(4):328-43
references: 23730257
references: Ann Neurol. 2000 Nov;48(5):766-73
references: 11079540
references: Neuron Glia Biol. 2011 May;7(2-4):129-41
references: 22613021
references: Neurobiol Aging. 1995 Jan-Feb;16(1):53-7
references: 7723936
references: J Neurochem. 2007 Feb;100(3):790-801
references: 17263797
references: Pediatr Neurol. 2007 Jan;36(1):25-9
references: 17162193
references: J Neurochem. 2006 Aug;98(3):916-25
references: 16771835
references: Ann Indian Acad Neurol. 2009 Jul;12(3):140-53
references: 20174493
references: J Exp Med. 1994 Dec 1;180(6):2297-308
references: 7964502
references: Nature. 2014 Mar 27;507(7493):423-5
references: 24678540
references: Cell Mol Biol (Noisy-le-grand). 2005 Sep 05;51(3):293-8
references: 16191397
references: Neurobiol Dis. 2005 Mar;18(2):375-84
references: 15686966
references: Int J Mol Sci. 2013 Jan 14;14(1):1455-76
references: 23344052
references: Histol Histopathol. 2006 Apr;21(4):445-58
references: 16437390
references: Eur J Neurosci. 2007 Oct;26(8):2119-30
references: 17927776
references: J Neurosci. 2012 May 2;32(18):6391-410
references: 22553043
references: Br J Pharmacol. 2003 Jul;139(6):1228-34
references: 12871843
references: Prog Neurobiol. 1999 Apr;57(6):563-81
references: 10221782
references: Epilepsia. 2012 Nov;53(11):1887-97
references: 22984896
references: Oxid Med Cell Longev. 2013;2013:598493
references: 24454986
references: Brain. 2005 Oct;128(Pt 10):2396-407
references: 15958506
references: FEBS J. 2005 Mar;272(6):1307-12
references: 15752349
references: Neurology. 1999 Feb;52(3):453-72
references: 10025773
references: Epilepsy Res. 2010 Jan;88(1):23-45
references: 19850449
references: J Clin Neurophysiol. 1995 Jul;12(4):316-25
references: 7560020
references: Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12700-5
references: 15310848
references: Drug Discov Today Dis Models. 2008;5(1):19-25
references: 19444332
references: Prog Neurobiol. 2007 Feb;81(2):89-131
references: 17275978
references: Epilepsia. 2003;44(s10):34-9
references: 14511393
references: PLoS One. 2012;7(9):e45250
references: 23028880
references: Eur J Neurosci. 2002 Apr;15(7):1105-14
references: 11982622
references: Nitric Oxide. 2005 Mar;12(2):61-9
references: 15740979
references: Glia. 2005 Oct;52(1):36-46
references: 15892126
references: Ann Neurol. 2003 Jun;53(6):711-7
references: 12783416
references: Drug Metab Rev. 2000 Aug-Nov;32(3-4):377-85
references: 11139135
references: Eur J Neurosci. 2012 Nov;36(9):3194-203
references: 22943535
references: Neuroscience. 2000;101(3):563-70
references: 11113305
references: Epilepsy Res. 2013 Nov;107(1-2):75-81
references: 24054426
references: Epilepsia. 2007 Sep;48(9):1750-1755
references: 17555528
references: Neuroimmunomodulation. 1998 May-Aug;5(3-4):143-59
references: 9730680
references: Cell. 1988 Nov 18;55(4):601-10
references: 3180221
references: Annu Rev Pharmacol Toxicol. 2013;53:401-26
references: 23294312
references: CNS Neurol Disord Drug Targets. 2011 Feb;10(1):44-56
references: 21143139
references: Nat Clin Pract Neurol. 2007 Sep;3(9):505-16
references: 17805245
references: J Cereb Blood Flow Metab. 2000 Jun;20(6):956-66
references: 10894179
references: Br J Pharmacol. 1999 May;127(2):546-52
references: 10385257
references: J Mol Neurosci. 2007;33(3):268-77
references: 17952636
references: Glia. 2012 Aug;60(8):1191
references: 22696194
references: Free Radic Biol Med. 2004 Dec 15;37(12):1951-62
references: 15544915
references: Neurobiol Dis. 2006 Oct;24(1):128-43
references: 16860990
references: Ann N Y Acad Sci. 2002 May;957:341-4
references: 12074994
references: Prog Neurobiol. 1999 Dec;59(6):663-90
references: 10845757
references: Cell Mol Immunol. 2006 Feb;3(1):63-6
references: 16549052
references: Epilepsia. 2004 Oct;45(10):1202-9
references: 15461674
references: FASEB J. 1990 Apr 1;4(6):1624-33
references: 2180770
references: CNS Drugs. 2002;16(10):669-94
references: 12269861
references: J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Nov 15;827(1):65-75
references: 16183338
references: J Cereb Blood Flow Metab. 2003 Feb;23(2):137-49
references: 12571445
references: Epilepsia. 1997 May;38(5):614-8
references: 9184609
references: J Neurosci. 2006 Oct 11;26(41):10514-23
references: 17035536
references: Mol Aspects Med. 1993;14(3):191-7
references: 8264333
references: J Bioenerg Biomembr. 2010 Dec;42(6):449-55
references: 21132357
references: Redox Biol. 2013 Dec 25;2:82-90
references: 24494187
references: Free Radic Res. 1999 Dec;31(6):651-69
references: 10630688
references: Neurotoxicology. 2012 Jun;33(3):500-11
references: 22387230
references: FASEB J. 2003 Oct;17(13):1957-9
references: 12923073
references: J Neurophysiol. 2007 May;97(5):3660-9
references: 17376845
references: Nutr Neurosci. 2004 Feb;7(1):33-9
references: 15085556
references: Pharmacol Biochem Behav. 2003 Feb;74(3):579-85
references: 12543222
references: Histol Histopathol. 2010 Jul;25(7):841-56
references: 20503173
references: Neurobiol Dis. 2012 Mar;45(3):1068-76
references: 22200564
references: Free Radic Res. 1999 Oct;31(4):261-72
references: 10517532
references: Pharmacol Ther. 2005 Mar;105(3):229-66
references: 15737406
references: Brain. 2008 Aug;131(Pt 8):2061-70
references: 18669513
references: Neurochem Int. 2007 Jan;50(2):379-85
references: 17074421
references: Eur J Clin Nutr. 2010 Nov;64 Suppl 3:S112-20
references: 21045839
references: Free Radic Biol Med. 2001 Dec 1;31(11):1287-312
references: 11728801
references: Neurochem Res. 2012 Nov;37(11):2339-50
references: 22488332
references: Epilepsia. 2006 Jul;47(7):1160-8
references: 16886979
references: Neurobiol Dis. 2011 Sep;43(3):706-14
references: 21669285
references: Antioxid Redox Signal. 2014 Jul 1;21(1):86-102
references: 24359220
references: Ann Nutr Metab. 2012;60 Suppl 3:27-36
references: 22614816
references: Biochem J. 1994 Mar 1;298 ( Pt 2):249-58
references: 7510950
references: J Neurosci. 2012 Aug 15;32(33):11250-8
references: 22895709
references: Lancet. 1993 Jun 26;341(8861):1607-10
references: 8099987
references: J Biochem. 2001 Aug;130(2):169-75
references: 11481032
references: Science. 1999 Jun 11;284(5421):1845-8
references: 10364559
references: J Mol Neurosci. 2009 Sep;39(1-2):9-21
references: 19130308
references: Epilepsy Res. 2002 Feb;48(3):157-68
references: 11904234
references: J Neurosci. 2011 Oct 19;31(42):14850-60
references: 22016518
references: Neurology. 1994 Apr;44(4):601-8
references: 8164811
references: Antioxid Redox Signal. 2006 Sep-Oct;8(9-10):1583-96
references: 16987013
references: Epilepsy Behav. 2009 May;15(1):10-4
references: 19236943
references: Mol Pharmacol. 1995 Jun;47(6):1189-96
references: 7603459
references: Seizure. 2010 Apr;19(3):165-72
references: 20149694
references: Biochem J. 2001 Aug 1;357(Pt 3):593-615
references: 11463332
references: Neurosci Lett. 2007 Apr 18;416(3):227-30
references: 17383094
references: Ann N Y Acad Sci. 2001 Jun;939:200-15
references: 11462772
references: Brain Res. 1996 May 13;720(1-2):75-83
references: 8782899
references: J Neurosci. 2007 Oct 3;27(40):10674-84
references: 17913901
references: Ann Neurol. 2004 Apr;55(4):576-80
references: 15048898
references: Neurosci Lett. 2007 Jun 8;420(1):76-9
references: 17512118
references: J Neurosci. 2006 Sep 6;26(36):9312-22
references: 16957087
references: Nat Rev Drug Discov. 2010 Jan;9(1):68-82
references: 20043029
references: Trends Neurosci. 1997 Dec;20(12):570-7
references: 9416670
references: CNS Neurol Disord Drug Targets. 2006 Oct;5(5):561-8
references: 17073658
references: Neurotherapeutics. 2010 Oct;7(4):494-506
references: 20880511
references: Adv Exp Med Biol. 1998;454:7-16
references: 9889871
references: Brain Res Bull. 2013 Mar;92:60-8
references: 23270878
references: Cell Mol Life Sci. 2012 Jul;69(14):2387-407
references: 22643836
references: Brain Res Bull. 2007 Jan 9;71(4):372-5
references: 17208654
references: J Neurochem. 2005 Jan;92(1):123-31
references: 15606902
references: J Neurotrauma. 1995 Oct;12(5):853-70
references: 8594213
references: Brain Res Bull. 1994;35(5-6):403-7
references: 7532097
references: Toxicol Ind Health. 1993 Jan-Apr;9(1-2):39-51
references: 8380305
references: Acta Neurol Scand. 2008 Nov;118(5):281-90
references: 18341684
references: Antioxid Redox Signal. 2004 Apr;6(2):289-300
references: 15025930
references: Epilepsia. 2002 Jul;43(7):703-10
references: 12102672
references: Amino Acids. 2012 Jan;42(1):181-97
references: 21399919
references: J Biomed Sci. 2011 Oct 20;18:75
references: 22014163
references: Korean J Physiol Pharmacol. 2009 Aug;13(4):265-71
references: 19885009
references: Glia. 2001 Nov;36(2):180-90
references: 11596126
references: Epilepsy Res. 2002 Apr;49(2):109-20
references: 12049799
references: FASEB J. 1992 Jun;6(9):2675-83
references: 1612291
references: Biochim Biophys Acta. 1991 Feb 19;1091(3):310-6
references: 2001414
references: Epilepsia. 2010 Aug;51(8):1395-402
references: 20477852
references: J Neurosci Res. 1998 Nov 1;54(3):382-9
references: 9819143
references: Epilepsy Res. 2000 Mar;39(1):63-71
references: 10690755
references: Trends Cardiovasc Med. 2002 Feb;12(2):62-6
references: 11852252
references: Neuroreport. 2001 Jun 13;12(8):1705-8
references: 11409743
references: Free Radic Biol Med. 2000 Feb 15;28(4):505-13
references: 10719231
references: Clin Biochem. 2007 Mar;40(5-6):292-8
references: 17291480
references: EMBO J. 1995 Apr 18;14(8):1590-8
references: 7737111
references: Curr Opin Clin Nutr Metab Care. 2008 Mar;11(2):113-20
references: 18301085
references: Neurosci Lett. 2000 Sep 22;291(3):179-82
references: 10984636
references: J Neurosci. 1999 Jun 15;19(12):5054-65
references: 10366638
references: CNS Neurol Disord Drug Targets. 2010 Jul;9(3):373-82
references: 20053169
references: Pharmacol Biochem Behav. 2008 Mar;89(1):1-5
references: 18096215
references: Seizure. 2012 Sep;21(7):508-11
references: 22652071
references: Nature. 1998 Jan 15;391(6664):281-5
references: 9440691
references: Epilepsy Curr. 2003 Sep;3(5):166-167
references: 15346167
references: J Neurochem. 2010 Dec;115(5):1172-82
references: 21219330
references: J Neurochem. 2001 Dec;79(5):1065-9
references: 11739620
references: Eur J Pharmacol. 2011 Oct 1;668(1-2):65-71
references: 21745465
references: Free Radic Biol Med. 2003 Jan 15;34(2):145-69
references: 12521597
references: Seizure. 2012 Dec;21(10):780-4
references: 23031823
references: J Mol Neurosci. 2010 Nov;42(3):359-69
references: 20369387
references: J Pathol. 2004 Nov;204(4):428-37
references: 15495269
references: J Neurosci Res. 2006 May 1;83(6):1088-105
references: 16493685
references: Epilepsy Res. 2013 Dec;107(3):306-10
references: 24139856
references: Neurochem Res. 2008 Jan;33(1):43-50
references: 17616813
references: J Clin Neurophysiol. 1999 Jul;16(4):341-52; discussion 353
references: 10478707
references: Neuroscience. 2003;118(2):431-7
references: 12699779
references: Exp Brain Res. 1996 May;109(2):251-67
references: 8738374
references: Int J Mol Sci. 2013 Jun 25;14(7):13109-28
references: 23799363
references: Free Radic Biol Med. 2013 Sep;62:121-131
references: 23411150
references: Pharmacogn Rev. 2010 Jul;4(8):118-26
references: 22228951
references: J Pharmacol Sci. 2004 Dec;96(4):465-73
references: 15599098
references: Free Radic Biol Med. 1995 Jun;18(6):993-1002
references: 7628735
references: J Neurosci. 2002 Aug 1;22(15):6650-8
references: 12151544
references: J Biol Chem. 1997 Feb 21;272(8):4959-63
references: 9030556
references: Acta Neurol Scand. 2000 Sep;102(3):179-88
references: 10987378
references: N Engl J Med. 2011 Sep 8;365(10):919-26
references: 21899452
references: Biochemistry (Mosc). 2004 Aug;69(8):844-54
references: 15377263
references: Life Sci. 2006 May 30;79(1):1-7
references: 16434059
references: Mol Cells. 2011 Dec;32(6):491-509
references: 22207195
references: N Engl J Med. 2000 Feb 3;342(5):314-9
references: 10660394
references: Neurochem Int. 2011 Aug;59(2):122-37
references: 21672578