Mitochondrial involvement and oxidative stress in temporal lobe epilepsy

Free Radical Biology and Medicine

Volumn 62, Issue , 2013, Pages 121-131

  Rowley, Shane ^a   Patel, Manisha ^a  

^a UNIVERSITY OF COLORADO   (United States)

Author keywords

Epilepsy; Free radicals; Mitochondria; Neurodegeneration; Reactive oxygen; Seizure

Indexed keywords

MITOCHONDRIAL DNA; REACTIVE OXYGEN METABOLITE;

DNA DAMAGE; EPILEPTOGENESIS; HUMAN; LIPID PEROXIDATION; MACROMOLECULE; METABOLISM; MITOCHONDRION; NONHUMAN; OXIDATION REDUCTION REACTION; OXIDATIVE STRESS; PRIORITY JOURNAL; REVIEW; SEIZURE; STEADY STATE; TEMPORAL LOBE EPILEPSY;

ANIMALIA;

EID: 84884906665     PISSN: 08915849     EISSN: 18734596     Source Type: Journal    
DOI: 10.1016/j.freeradbiomed.2013.02.002     Document Type: Review

References (106)

1. Hauser, W. A.; Annegers, J. F. Risk factors for epilepsy. Epilepsy Res. Suppl. 4: 45-52; 1991.
2. Liang, L. P.; Ho, Y. S.; Patel, M. Mitochondrial superoxide production in kainate-induced hippocampal damage. Neuroscience 101: 563-570; 2000.
3. Patel, M.; Liang, L. P.; Roberts, L. J. Enhanced hippocampal F2-isoprostane formation following kainate-induced seizures. J. Neurochem. 79: 1065-1069; 2001. (Pubitemid 33117087)
4. Jarrett, S. G.; Milder, J. B.; Liang, L. -P.; Patel, M. The ketogenic diet increases mitochondrial glutathione levels. J. Neurochem. 106: 1044-1051; 2008.
5. Garriga-Canut, M.; Schoenike, B.; Qazi, R.; Bergendahl, K.; Daley, T. J.; Pfender, R. M.; Morrison, J. F.; Ockuly, J.; Stafstrom, C.; Sutula, T.; Roopra, A. 2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure. Nat. Neurosci. 9: 1382-1387; 2006. (Pubitemid 44646210)
6. Rahman, S. Mitochondrial disease and epilepsy. Dev. Med. Child Neurol. 54: 397-406; 2012.
7. Kawai, N.; Miyake, K.; Kuroda, Y.; Yamashita, S.; Nishiyama, Y.; Monden, T.; Sasakawa, Y.; Nagao, S. Magnetic resonance imaging and positron emission tomography findings in status epilepticus following severe hypoglycemia. Ann. Nucl. Med. 20: 371-376; 2006. (Pubitemid 44099130)
8. Vielhaber, S.; Niessen, H. G.; Debska-Vielhaber, G.; Kudin, A. P.; Wellmer, J.; Kaufmann, J.; Schönfeld, M. A.; Fendrich, R.; Willker, W.; Leibfritz, D.; Schramm, J.; Elger, C. E.; Heinze, H. -J.; Kunz, W. S. Subfield-specific loss of hippocampal N-acetyl aspartate in temporal lobe epilepsy. Epilepsia 49: 40-50; 2008.
9. Savic, I.; Thomas, A. M.; Ke, Y.; Curran, J.; Fried, I.; Engel, J. In vivo measurements of glutamine+glutamate (Glx) and N-acetyl aspartate (NAA) levels in human partial epilepsy. Acta Neurol. Scand. 102: 179-188; 2000. (Pubitemid 30645136)
10. Kann, O.; Kovacs, R.; Njunting, M.; Behrens, C. J.; Otahal, J.; Lehmann, T. -N.; Gabriel, S.; Heinemann, U. Metabolic dysfunction during neuronal activation in the ex vivo hippocampus from chronic epileptic rats and humans. Brain 128(Pt 10): 2396-2407; 2005. (Pubitemid 41407978)
11. Meldrum, B. S. Excitotoxicity and selective neuronal loss in epilepsy. Brain Pathol. (Zurich) 3: 405-412; 1993. (Pubitemid 23349811)
12. Kilany, A.; Raouf, E. R. A.; Gaber, A. A.; Aloush, T. K.; Aref, H. A.; Anwar, M.; Henshall, D. C; Abdulghani, M. O. Elevated serum Bcl-2 in children with temporal lobe epilepsy. Seizure 21: 250-253; 2012.
13. Henshall, D. C; Clark, R. S.; Adelson, P. D.; Chen, M.; Watkins, S. C; Simon, R. P. Alterations in bcl-2 and caspase gene family protein expression in human temporal lobe epilepsy. Neurology 55: 250-257; 2000. (Pubitemid 30604626)
14. Duchen, M. R. Mitochondria and calcium: from cell signalling to cell death. J. Physiol. 529(Pt 1): 57-68; 2000.
15. Chuang, Y. -C; Chen, S. -D.; Liou, C. -W.; Lin, T. -K.; Chang, W. -N.; Chan, S. H. H.; Chang, A. Y. W. Contribution of nitric oxide, superoxide anion, and peroxynitrite to activation of mitochondrial apoptotic signaling in hippo-campal CA3 subfield following experimental temporal lobe status epilepti-cus. Epilepsia 50: 731-746; 2009.
16. Kovacs, R.; Kardos, J.; Heinemann, U.; Kann, O. Mitochondrial calcium ion and membrane potential transients follow the pattern of epileptiform discharges in hippocampal slice cultures. J. Neurosci 25: 4260-4269; 2005. (Pubitemid 40628770)
17. Jarrett, S. G.; Liang, L. -P.; Hellier, J. L.; Staley, K.J.; Patel, M.; Mitochondrial, DNA damage and impaired base excision repair during epileptogenesis. Neurobiol. Dis. 30: 130-138; 2008.
18. Kunz, W. S.; Kudin, A. P.; Vielhaber, S.; Blümcke, I.; Zuschratter, W.; Schramm, J.; Beck, H.; Elger, C. E. Mitochondrial complex I deficiency in the epileptic focus of patients with temporal lobe epilepsy. Ann. Neurol. 48: 766-773; 2000.
19. Mueller, S. G.; Trabesinger, A. H.; Boesiger, P.; Wieser, H. G. Brain glutathione levels in patients with epilepsy measured by in vivo 1H-MRS. Neurology 57: 1422-1427; 2001. (Pubitemid 32995723)
20. Baron, M.; Kudin, A. P.; Kunz, W. S. Mitochondrial dysfunction in neurodegenerative disorders. Biochem. Soc. Transact 35(Pt 5): 1228-1231; 2007. (Pubitemid 350206468)
21. O'Brien, T. J.; Newton, M. R.; Cook, M. J.; Berlangieri, S. U.; Kilpatrick, C; Morris, K.; Berkovic, S. F. Hippocampal atrophy is not a major determinant of regional hypometabolism in temporal lobe epilepsy. Epilepsia 38: 74-80; 1997. (Pubitemid 27057484)
22. Sashindranath, M.; McLean, K. J.; Trounce, I. A.; Cotton, R. G. H.; Cook, M. J. Early hippocampal oxidative stress is a direct consequence of seizures in the rapid electrical amygdala kindling model. Epilepsy Res. 90: 285-294; 2010.
23. Frantseva, M. V; Perez Velazquez, J. L.; Tsoraklidis, G.; Mendonca, A. J.; Adamchik, Y.; Mills, L. R.; Carlen, P. L.; Burnham, M. W. Oxidative stress is involved in seizure-induced neurodegeneration in the kindling model of epilepsy. Neuroscience 97: 431-435; 2000. (Pubitemid 30320750)
24. Gluck, M. R.; Jayatilleke, E.; Shaw, S.; Rowan, A. J.; Haroutunian, V. CNS oxidative stress associated with the kainic acid rodent model of experimental epilepsy. Epilepsy Res. 39: 63-71; 2000. (Pubitemid 30053124)
25. Peterson, S. L.; Morrow, D.; Liu, S.; Liu, K. J. Hydroethidine detection of superoxide production during the lithium-pilocarpine model of status epilepticus. Epilepsy Res. 49: 226-238; 2002. (Pubitemid 34657268)
26. Forster, M. J.; Dubey, A.; Dawson, K. M.; Stutts, W. A.; Lal, H.; Sohal, R. S. Age-related losses of cognitive function and motor skills in mice are associated with oxidative protein damage in the brain. Proc. Natl. Acad. Sci. USA 93: 4765-4769; 1996. (Pubitemid 26162825)
27. Floor, E.; Wetzel, M. G. Increased protein oxidation in human substantia nigra pars compacta in comparison with basal ganglia and prefrontal cortex measured with an improved dinitrophenylhydrazine assay. J. Neurochem 70: 268-275; 1998. (Pubitemid 28020852)
28. Bruce, A. J.; Baudry, M. Oxygen free radicals in rat limbic structures after kainate-induced seizures. Free Radic. Biol. Med. 18: 993-1002; 1995.
29. Gardner, P. R.; Fridovich, I.Inactivation-reactivation of aconitase in Escherichia coli: a sensitive measure of superoxide radical. J. Biol. Chem. 267: 8757-8763;1992.
30. Gardner, P. R.; Costantino, G.; Szabo, C; Salzman, A. L. Nitric oxide sensitivity of the aconitases. J. Biol. Chem. 272: 25071-25076; 1997. (Pubitemid 27415688)
31. Liang, L. -P.; Patel, M. Mitochondrial oxidative stress and increased seizure susceptibility in Sod2 (-/+) mice. Free Radic. Biol. Med. 36: 542-554; 2004. (Pubitemid 38230173)
32. Cock, H. R.; Tong,X.; Hargreaves, I. P.; Heales, S.J. R.; Clark,J. B.; Patsalos, P. N.; Thom, M.; Groves, M.; Schapira, A. H. V; Shorvon, S. D.; Walker, M. C. Mitochondrial dysfunction associated with neuronal death following status epilepticus in rat. Epilepsy Res. 48: 157-168; 2002. (Pubitemid 34252900)
33. Wallace, D. C. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu. Rev. Genet. 39: 359-407; 2005. (Pubitemid 43011120)
34. Ryan, K.; Backos, D. S.; Reigan, P.; Patel, M. Post-translational oxidative modification and inactivation of mitochondrial complex I in epileptogenesis. J. Neurosci. 32: 11250-11258; 2012.
35. Liang, L. -P.; Jarrett, S. G.; Patel, M. Chelation of mitochondrial iron prevents seizure-induced mitochondrial dysfunction and neuronal injury. J. Neurosci. 28: 11550-11556; 2008.
36. Gerlach, M.; Ben-Shachar, D.; Riederer, P.; Youdim, M. B. Altered brain metabolism of iron as a cause of neurodegenerative diseases? J. Neurochem. 63: 793-807; 1994. (Pubitemid 24266591)
37. Lee, D. W.; Andersen, J. K. Iron elevations in the aging Parkinsonian brain: a consequence of impaired iron homeostasis? J. Neurochem. 112: 332-339; 2010.
38. Amici, A.; Levine, R. L.; Tsai, L.; Stadtman, E. R. Conversion of amino acid residues in proteins and amino acid homopolymers to carbonyl derivatives by metal-catalyzed oxidation reactions. J. Biol. Chem. 264: 3341-3346; 1989. (Pubitemid 19063388)
39. Kudin, A. P.; Bimpong-Buta, N. Y. -B.; Vielhaber, S.; Elger, C. E.; Kunz, W. S. Characterization of superoxide-producing sites in isolated brain mitochondria. J. Biol. Chem. 279: 4127-4135; 2004. (Pubitemid 38198997)
40. Fato, R.; Bergamini, C.; Bortolus, M.; Maniero, A. L.; Leoni, S.; Ohnishi, T.; Lenaz, G. Differential effects of mitochondrial Complex I inhibitors on production of reactive oxygen species. Biochim. Biophys. Acta 384-3892: 2009; 1787.
41. Hirst, J. Towards the molecular mechanism of respiratory complex I. Biochem. J. 425: 327-339; 2010.
42. Murphy, M. P. How mitochondria produce reactive oxygen species. Biochem. J. 417: 1-13; 2009.
43. Rothstein, J. D.; Martin, L.; Levey, A. I.; Dykes-Hoberg, M.; Jin, L.; Wu, D.; Nash, N.; Kuncl, R. W. Localization of neuronal and glial glutamate transporters. Neuron 13: 713-725; 1994. (Pubitemid 24300175)
44. Frizzo, M. E.; Frizzo, J. K.; Amadio, S.; Rodrigues, J. M.; Perry, M. L.; Bernardi, G.; Volonté, C. Extracellular adenosine triphosphate induces glutamate transporter-1 expression in hippocampus. Hippocampus 17: 305-315; 2007. (Pubitemid 46649582)
45. Trotti, D.; Danbolt, N. C.; Volterra, A. Glutamate transporters are oxidant-vulnerable: a molecular link between oxidative and excitotoxic neurode-generation? Trends Pharmacol. Sci. 19: 328-334; 1998. (Pubitemid 28389731)
46. Meldrum, B. S.; Akbar, M. T.; Chapman, A. G. Glutamate receptors and transporters in genetic and acquired models of epilepsy. Epilepsy Res. 36: 189-204; 1999. (Pubitemid 29457580)
47. Tritschler, H. J.; Medori, R.; Mitochondrial, DNA alterations as a source of human disorders. Neurology 43: 280-288; 1993. (Pubitemid 23060256)
48. Esposito, L. A.; Melov, S.; Panov, A.; Cottrell, B. A.; Wallace, D. C. Mitochon-drial disease in mouse results in increased oxidative stress. Proc. Natl. Acad. Sci. USA 96: 4820-4825; 1999. (Pubitemid 29214495)
49. Bohr, V. A.; Stevnsner, T.; de Souza-Pinto, N. C. Mitochondrial DNA repair of oxidative damage in mammalian cells. Gene 286: 127-134; 2002. (Pubitemid 34273869)
50. Kudin, A. P.; Kudina, T. A.; Seyfried, J.; Vielhaber, S.; Beck, H.; Elger, C. E.; Kunz, W. S. Seizure-dependent modulation of mitochondrial oxidative phosphorylation in rat hippocampus. Eur. J. Neurosci. 15: 1105-1114; 2002. (Pubitemid 35463612)
51. Dizdaroglu, M. Chemical determination of free radical-induced damage to DNA. Free Radic. Biol. Med. 10: 225-242; 1991. (Pubitemid 121003232)
52. Halliwell, B.; Gutteridge, J. M. Oxygen free radicals and iron in relation to biology and medicine: some problems and concepts. Arch. Biochem. Biophys. 246: 501-514; 1986. (Pubitemid 16072574)
53. Coyle, J. T.; Puttfarcken, P. Oxidative stress, glutamate, and neurodegenera-tive disorders. Science 262: 689-695; 1993. (Pubitemid 23350687)
54. Eraković, V.; Zupan, G.; Mrsić, J.; Simonić, A.; Varljen, J. The influence of nicardipine and ifenprodil on the brain free arachidonic acid level and behavior in hypoxia-exposed rats. Prog. Neuro-psychopharmacol. Biol. Psychiatry 21: 633-647; 1997. (Pubitemid 27244174)
55. Mrsić, J.; Zupan, G.; Eraković, V.; Simonić, A.; Varljen, J. The influence of nimodipine and MK-801 on the brain free arachidonic acid level and the learning ability in hypoxia-exposed rats. Prog. Neuro-psychopharmacol. Biol. Psychiatry 21: 345-358; 1997. (Pubitemid 27149396)
56. Roberts, L. J.; Morrow, J. D. Measurement of F(2)-isoprostanes as an index of oxidative stress in vivo. Free Radic. Biol. Med. 28: 505-513; 2000. (Pubitemid 30136031)
57. Patel, M.; Liang, L. -P.; Hou, H.; Williams, B. B.; Kmiec, M.; Swartz, H. M.; Fessel, J. P.; Roberts, L. J. Seizure-induced formation of isofurans: novel products of lipid peroxidation whose formation is positively modulated by oxygen tension. J. Neurochem. 104: 264-270; 2008. (Pubitemid 350265056)
58. Cini, M.; Moretti, A. Studies on lipid peroxidation and protein oxidation in the aging brain. Neurobiol. Aging 16: 53-57; 1995.
59. Tejada, S.; Sureda, A.; Roca, C.; Gamundí, A.; Esteban, S. Antioxidant response and oxidative damage in brain cortex after high dose of pilocar-pine. Brain Res. Bull. 71: 372-375; 2007. (Pubitemid 46043411)
60. Reed, D. J.; Savage, M. K. Influence of metabolic inhibitors on mitochondrial permeability transition and glutathione status. Biochim. Biophys. Acta 1271: 43-50; 1995.
61. Liang, L. -P.; Patel, M. Seizure-induced changes in mitochondrial redox status. Free Radic. Biol. Med. 40: 316-322; 2006. (Pubitemid 43069355)
62. O'Donovan, D. J.; Rogers, L. K.; Kelley, D. K.; Welty, S. E.; Ramsay, P. L.; Smith, C. V CoASH and CoASSG levels in lungs of hyperoxic rats as potential biomarkers of intramitochondrial oxidant stresses. Pediatr. Res. 51: 346-353; 2002. (Pubitemid 34174972)
63. Waldbaum, S.; Liang, L. -P.; Patel, M. Persistent impairment of mitochon-drial and tissue redox status during lithium-pilocarpine-induced epilepto-genesis. J. Neurochem. 115: 1172-1182; 2010.
64. Sudha, K.; Rao, A. V; Rao, A. Oxidative stress and antioxidants in epilepsy. Clin. Chim. Acta 303: 19-24; 2001. (Pubitemid 32121801)
65. Carlsson, L. M.; Jonsson, J.; Edlund, T.; Marklund, S. L. Mice lacking extracellular superoxide dismutase are more sensitive to hyperoxia. Proc. Natl. Acad. Sci. USA 92: 6264-6268; 1995.
66. Reaume, A. G.; Elliott, J. L.; Hoffman, E. K.; Kowall, N. W.; Ferrante, R. J.; Siwek, D. F.; Wilcox, H. M.; Flood, D. G.; Beal, M. F.; Brown, R. H.; Scott, R. W.; Snider, W. D. Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury. Nat. Genet. 13: 43-47; 1996. (Pubitemid 26139292)
67. Li, Y.; Huang, T. T.; Carlson, E. J.; Melov, S.; Ursell, P. C; Olson, J. L.; Noble, L. J.; Yoshimura, M. P.; Berger, C; Chan, P. H.; Wallace, D. C; Epstein, C.J. Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Nat. Genet. 11: 376-381; 1995.
68. Huang, T. T.; Carlson, E. J.; Kozy, H. M.; Mantha, S.; Goodman, S. I.; Ursell, P. C; Epstein, C. J. Genetic modification of prenatal lethality and dilated cardiomyopathy in Mn superoxide dismutase mutant mice. Free Radic. Biol. Med. 31: 1101-1110; 2001. (Pubitemid 33000132)
69. Patel, M. N. Metalloporphyrins improve the survival of Sod2-deficient neurons. Aging Cell 2: 219-222; 2003.
70. Patel, M.; Li, Q. -Y.; Chang, L. -Y.; Crapo, J.; Liang, L -P. Activation of NADPH oxidase and extracellular superoxide production in seizure-induced hippo- campal damage. J. Neurochem. 92: 123-131; 2005. (Pubitemid 40193515)
71. Hwang, J.; Saha, A.; Boo, Y. C; Sorescu, G. P.; McNally, J. S.; Holland, S. M.; Dikalov, S.; Giddens, D. P.; Griendling, K. K.; Harrison, D. G.; Jo, H. Oscillatory shear stress stimulates endothelial production of O^" from p47phox-dependent NAD(P)H oxidases, leading to monocyte adhesion. J. Biol. Chem. 278: 47291-47298; 2003. (Pubitemid 37452318)
72. Liang, L. -P.; Waldbaum, S.; Rowley, S.; Huang, T. -T.; Day, B. J.; Patel, M. Mitochondrial oxidative stress and epilepsy in SOD2 deficient mice: attenuation by a lipophilic metalloporphyrin. Neurobiol. Dis. 45: 1068-1076; 2012.
73. James, A. M.; Murphy, M. P. How mitochondrial damage affects cell function. J. Biomed. Sci. 9(Pt 1): 475-487; 2002. (Pubitemid 35316860)
74. Galella, G.; Turano, C; Girvin, J. Metabolic changes in the hippocampus after prolonged epileptic discharge. J. Neurosurg. Sci. 27: 69-71; 1983. (Pubitemid 13020276)
75. Handforth, A.; Treiman, D. M. Functional mapping of the late stages of status epilepticus in the lithium-pilocarpine model in rat: a 14C-2-deoxyglucose study. Neuroscience 64: 1075-1089; 1995.
76. Folbergrova, J.; Ingvar, M.; Nevander, G.; Siesjo, B. K. Cerebral metabolic changes during and following fluorothyl-induced seizures in ventilated rats. J. Neurochem. 44: 1419-1426; 1985. (Pubitemid 15056909)
77. Nakamoto, Y.; Nakayama, S.; Suzuki, J. Cerebral uptake of [14C]deoxyglucose during the entire seizure and the recovery period in an El mouse. Epilepsy Res 5: 43-48; 1990. (Pubitemid 20046591)
78. Nishikawa, T.; Edelstein, D.; Du, X. L.; Yamagishi, S.; Matsumura, T.; Kaneda, Y.; Yorek, M. A.; Beebe, D.; Oates, P. J.; Hammes, H. P.; Giardino, I.; Brownlee, M. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404: 787-790; 2000. (Pubitemid 30212409)
79. Erecinska, M.; Silver, I. A. Ions and energy in mammalian brain. Prog. Neurobiol. 43: 37-71; 1994. (Pubitemid 24221854)
80. Grisar, T. Glial and neuronal Na+-K+ pump in epilepsy. Ann. Neurol. 16(Suppl):S128-134; 1984.
81. Gulyas, A. I.; Buzsaki, G.; Freund, T. F.; Hirase, H. Populations of hippocam- pal inhibitory neurons express different levels of cytochrome c. Eur. J. Neurosci. 23: 2581-2594; 2006. (Pubitemid 43801450)
82. Verstreken, P.; Ly, C. V; Venken, K. J. T.; Koh, T. -W.; Zhou, Y.; Bellen, H. J. Synaptic mitochondria are critical for mobilization of reserve pool vesicles at Drosophila neuromuscular junctions. Neuron 47: 365-378; 2005. (Pubitemid 41073878)
83. Vesce, S.; Jekabsons, M. B.; Johnson-Cadwell, L. I.; Nicholls, D. G. Acute glutathione depletion restricts mitochondrial ATP export in cerebellar granule neurons. J. Biol. Chem. 280: 38720-38728; 2005. (Pubitemid 43853775)
84. Yadava, N.; Nicholls, D. G. Spare respiratory capacity rather than oxidative stress regulates glutamate excitotoxicity after partial respiratory inhibition of mitochondrial complex I with rotenone. J. Neurosci 27: 7310-7317; 2007. (Pubitemid 47037569)
85. S. Kovac, A. Y. Abramov, M. C. Walker, Energy depletion in seizures: anaplerosis as a strategy for future therapies. Neuropharmacology http://dx.doi.org/10. 1016/j.neuropharm.2012.05.012, in press.
86. Cantu, D.; Schaack, J.; Patel, M. Oxidative inactivation of mitochondrial aconitase results in iron and H2O2-mediated neurotoxicity in rat primary mesencephalic cultures. PLoS One 4:e7095; 2009.
87. Cantu, D.; Fulton, R. E.; Drechsel, D. A.; Patel, M. Mitochondrial aconitase knockdown attenuates paraquat-induced dopaminergic cell death via decreased cellular metabolism and release of iron and H2O2. J. Neurochem. 118: 79-92; 2011.
88. Thiele, E. A. Assessing the efficacy of antiepileptic treatments: the ketogenic diet. Epilepsia 44(Suppl. 7): 26-29; 2003. (Pubitemid 37100026)
89. Schwechter, E. M.; Velískova, J.; Velísek, L. Correlation between extracellular glucose and seizure susceptibility in adult rats. Ann. Neurol. 53: 91-101; 2003. (Pubitemid 36083833)
90. Bough, K. J.; Wetherington, J.; Hassel, B.; Pare, J. F.; Gawryluk, J. W.; Greene, J. G.; Shaw, R.; Smith, Y.; Geiger, J. D.; Dingledine, R. J. Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet. Ann. Neurol. 60: 223-235; 2006. (Pubitemid 44182397)
91. Maalouf, M.; Sullivan, P. G.; Davis, L.; Kim, D. Y.; Rho, J. M. Ketones inhibit mitochondrial production of reactive oxygen species production following glutamate excitotoxicity by increasing NADH oxidation. Neuroscience 145: 256-264; 2007. (Pubitemid 46227735)
92. Stafstrom, C. E.; Ockuly, J. C; Murphree, L.; Valley, M. T.; Roopra, A.; Sutula, T. P. Anticonvulsant and antiepileptic actions of 2-deoxy-D-glucose in epilepsy models. Ann. Neurol. 65: 435-447; 2009.
93. Weindruch, R.; Naylor, P. H.; Goldstein, A. L.; Walford, R. L. Influences of aging and dietary restriction on serum thymosin alpha 1 levels in mice. J. Gerontol. 43:B40-42; 1988. (Pubitemid 18080907)
94. Gasior, M.; Yankura, J.; Hartman, A. L.; French, A.; Rogawski, M. A. Antic-onvulsant and proconvulsant actions of 2-deoxy-D-glucose. Epilepsia 51: 1385-1394; 2010.
95. Vexler, Z. S.; Wong, A.; Francisco, C.; Manabat, C.; Christen, S.; Täuber, M.; Ferriero, D. M.; Gregory, G. Fructose-1,6-bisphosphate preserves intracel-lular glutathione and protects cortical neurons against oxidative stress. Brain Res. 960: 90-98; 2003. (Pubitemid 36044566)
96. Lian, X. -Y.; Khan, F. A.; Stringer, J. L. Fructose-1,6-bisphosphate has anticonvulsant activity in models of acute seizures in adult rats. J. Neurosci. 27: 12007-12011; 2007. (Pubitemid 350072086)
97. Giménez-Cassina, A.; Martínez-Franc-ois, J. R.; Fisher, J. K.; Szlyk, B.; Polak, K.; Wiwczar, J.; Tanner, G. R.; Lutas, A.; Yellen, G.; Danial, N. N. BAD-dependent regulation of fuel metabolism and K(ATP) channel activity confers resistance to epileptic seizures. Neuron 74: 719-730; 2012.
98. Gibbs, J. E.; Walker, M. C.; Cock, H. R. Levetiracetam: antiepileptic properties and protective effects on mitochondrial dysfunction in experimental status epilepticus. Epilepsia 47: 469-478; 2006. (Pubitemid 43351547)
99. Barros, D. O.; Xavier, S. M. L.; Barbosa, C. O.; Silva, R. F.; Freitas, R. L. M.; Maia, F. D.; Oliveira, A. A.; Freitas, R. M.; Takahashi, R. N. Effects of the vitamin E in catalase activities in hippocampus after status epilepticus induced by pilocarpine in Wistar rats. Neurosci. Lett. 416: 227-230; 2007. (Pubitemid 46509481)
100. Ogunmekan, A. O.; Hwang, P. A. A randomized, double-blind, placebo-controlled, clinical trial of D-alpha-tocopheryl acetate (vitamin E), as add-on therapy, for epilepsy in children. Epilepsia 30: 84-89; 1989. (Pubitemid 19056019)
101. Levy, S. L.; Burnham, W. M.; Bishai, A.; Hwang, P. A. The anticonvulsant effects of vitamin E: a further evaluation. Can. J. Neurol. Sci. 19: 201-203; 1992.
102. Xu, K.; Stringer, J. L. Antioxidants and free radical scavengers do not consistently delay seizure onset in animal models of acute seizures. Epilepsy Behav 13: 77-82; 2008.
103. Patel, M.; Day, B. J. Metalloporphyrin class of therapeutic catalytic anti-oxidants. Trends Pharmacol. Sci. 20: 359-364; 1999. (Pubitemid 29421616)
104. Melov, S.; Doctrow, S. R.; Schneider, J. A.; Haberson, J.; Patel, M.; Coskun, P. E.; Huffman, K.; Wallace, D. C.; Malfroy, B. Lifespan extension and rescue of spongiform encephalopathy in superoxide dismutase 2 nullizygous mice treated with superoxide dismutase-catalase mimetics. J. Neurosci. 21: 8348-8353; 2001. (Pubitemid 33051432)
105. Rong, Y.; Doctrow, S. R.; Tocco, G.; Baudry, M. EUK-134, a synthetic superoxide dismutase and catalase mimetic, prevents oxidative stress and attenuates kainate-induced neuropathology. Proc. Natl. Acad. Sci. USA 96: 9897-9902; 1999. (Pubitemid 29398829)
106. Brand, M. D.; Nicholls, D. G. Assessing mitochondrial dysfunction in cells. Biochem. J. 435: 297-312; 2011.