Preconditioning for Epilepsy

  • David C. HenshallEmail author
  • Eva M. Jimenez-Mateos
Part of the Springer Series in Translational Stroke Research book series (SSTSR)


Epilepsy is a common, chronic neurologic disorder characterised by recurrent, unprovoked seizures. Although most seizures stop within a few minutes, prolonged seizures (status epilepticus) can develop if normal mechanisms of seizure termination fail. Status epilepticus can cause substantial neuronal death within various brain structures, including the hippocampus. Brief or repeated mild seizures delivered prior to status epilepticus can, however, serve as preconditioning, thus rendering brain regions temporarily less susceptible to damage. Epileptic tolerance has been demonstrated using a variety of seizure-preconditioning paradigms, including electroconvulsive shocks and low doses of excitotoxins such as kainic acid. Transcription factors, growth factors and apoptosis-associated genes have been implicated. Transcriptome profiling has further revealed a novel genomic response which, like that of ischemic tolerance, features predominantly gene downregulation. The affected processes include transport, calcium signalling and neurotransmission, suggesting epileptic tolerance is acquired via generation of an anti-excitotoxicity phenotype. This chapter summarises the various animal models of epileptic tolerance, proposed effector(s) and future challenges in what has become an important experimental tool for identifying novel targets for neuroprotection and anti-epileptogenesis.


Status Epilepticus Kainic Acid Ischemic Tolerance Spontaneous Seizure Tolerance Model 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors thank Martha B. Johnson and Roger P. Simon for support with comparative bioinformatics between ischemic and epileptic tolerance and Suzanne Miller-Delaney for careful editing. The authors wish to acknowledge the support of Science Foundation Ireland (08/IN1/B1875).


  1. Akbar MT, Lundberg AM, Liu K, Vidyadaran S, Wells KE, Dolatshad H, Wynn S, Wells DJ, Latchman DS, De Belleroche J (2003) The neuroprotective effects of heat shock protein 27 overexpression in transgenic animals against kainate-induced seizures and hippocampal cell death. J Biol Chem 278:19956–19965PubMedCrossRefGoogle Scholar
  2. Andre V, Ferrandon A, Marescaux C, Nehlig A (2000a) The lesional and epileptogenic consequences of lithium-pilocarpine-induced status epilepticus are affected by previous exposure to isolated seizures: effects of amygdala kindling and maximal electroshocks. Neuroscience 99:469–481PubMedCrossRefGoogle Scholar
  3. Andre V, Ferrandon A, Marescaux C, Nehlig A (2000b) Electroshocks delay seizures and subsequent epileptogenesis but do not prevent neuronal damage in the lithium-pilocarpine model of epilepsy. Epilepsy Res 42:7–22PubMedCrossRefGoogle Scholar
  4. Barton ME, Shannon HE (2005) The seizure-related phenotype of brain-derived neurotrophic factor knockdown mice. Neuroscience 136:563–569PubMedCrossRefGoogle Scholar
  5. Blondeau N, Plamondon H, Richelme C, Heurteaux C, Lazdunski M (2000) K(ATP) channel openers, adenosine agonists and epileptic preconditioning are stress signals inducing hippocampal neuroprotection. Neuroscience 100:465–474PubMedCrossRefGoogle Scholar
  6. Blondeau N, Widmann C, Lazdunski M, Heurteaux C (2001) Activation of the nuclear factor-kappaB is a key event in brain tolerance. J Neurosci 21:4668–4677PubMedGoogle Scholar
  7. Boeck CR, Ganzella M, Lottermann A, Vendite D (2004) NMDA preconditioning protects against seizures and hippocampal neurotoxicity induced by quinolinic acid in mice. Epilepsia 45:745–750PubMedCrossRefGoogle Scholar
  8. Boison D (2008a) The adenosine kinase hypothesis of epileptogenesis. Prog Neurobiol 84:249–262PubMedCrossRefGoogle Scholar
  9. Boison D (2008b) Adenosine as a neuromodulator in neurological diseases. Curr Opin Pharmacol 8:2–7PubMedCrossRefGoogle Scholar
  10. Borges K, Shaw R, Dingledine R (2007) Gene expression changes after seizure preconditioning in the three major hippocampal cell layers. Neurobiol Dis 26:66–77PubMedCrossRefGoogle Scholar
  11. Brecht S, Simler S, Vergnes M, Mielke K, Marescaux C, Herdegen T (1999) Repetitive electroconvulsive seizures induce activity of c-Jun N-terminal kinase and compartment-specific desensitization of c-Jun phosphorylation in the rat brain. Brain Res Mol Brain Res 68:101–108PubMedCrossRefGoogle Scholar
  12. Bumanglag AV, Sloviter RS (2008) Minimal latency to hippocampal epileptogenesis and clinical epilepsy after perforant pathway stimulation-induced status epilepticus in awake rats. J Comp Neurol 510:561–580PubMedCrossRefGoogle Scholar
  13. Chang BS, Lowenstein DH (2003) Epilepsy. N Engl J Med 349:1257–1266PubMedCrossRefGoogle Scholar
  14. Chen J, Graham SH, Zhu RL, Simon RP (1996) Stress proteins and tolerance to focal cerebral ischemia. J Cereb Blood Flow Metab 16:566–577PubMedCrossRefGoogle Scholar
  15. Chen K, Baram TZ, Soltesz I (1999) Febrile seizures in the developing brain result in persistent modification of neuronal excitability in limbic circuits. Nat Med 5:888–894PubMedCrossRefGoogle Scholar
  16. Chuang DM, Gao XM, Paul SM (1992) N-methyl-D-aspartate exposure blocks glutamate toxicity in cultured cerebellar granule cells. Mol Pharmacol 42:210–216PubMedGoogle Scholar
  17. de Araujo Herculano B, Vandresen-Filho S, Martins WC, Boeck CR, Tasca CI (2011) NMDA preconditioning protects against quinolinic acid-induced seizures via PKA, PI3K and MAPK/ERK signaling pathways. Behav Brain Res 219:92–97PubMedCrossRefGoogle Scholar
  18. DeLorenzo RJ (2006) Incidence and causes of status epilepticus. In: Wasterlain CG, Treiman DM (eds) Status Epilepticus: mechanisms and management. MIT Press, Cambridge, MA, pp 17–29Google Scholar
  19. Dieterich DC, Lee JJ, Link AJ, Graumann J, Tirrell DA, Schuman EM (2007) Labeling, detection and identification of newly synthesized proteomes with bioorthogonal non-canonical amino-acid tagging. Nat Protoc 2:532–540PubMedCrossRefGoogle Scholar
  20. Dirnagl U, Simon RP, Hallenbeck JM (2003) Ischemic tolerance and endogenous neuroprotection. Trends Neurosci 26:248–254PubMedCrossRefGoogle Scholar
  21. Dmowska M, Cybulska R, Schoenborn R, Piersiak T, Jaworska-Adamu J, Gawron A (2010) Behavioural and histological effects of preconditioning with lipopolysaccharide in epileptic rats. Neurochem Res 35(2):262–272PubMedCrossRefGoogle Scholar
  22. El Bahh B, Lurton D, Sundstrom LE, Rougier A (1997) Induction of tolerance and mossy fibre neuropeptide-Y expression in the contralateral hippocampus following a unilateral intrahippocampal kainic acid injection in the rat. Neurosci Lett 227:135–139PubMedCrossRefGoogle Scholar
  23. El Bahh B, Auvergne R, Lere C, Brana C, Le Gal La Salle G, Rougier A (2001) Decreased epileptic susceptibility correlates with neuropeptide Y overexpression in a model of tolerance to excitotoxicity. Brain Res 894:209–217PubMedCrossRefGoogle Scholar
  24. Emerson MR, Nelson SR, Samson FE, Pazdernik TL (1999) Hypoxia preconditioning attenuates brain edema associated with kainic acid-induced status epilepticus in rats. Brain Res 825:189–193PubMedCrossRefGoogle Scholar
  25. Engel T, Henshall DC (2009) Apoptosis, Bcl-2 family proteins and caspases: the ABCs of seizure-damage and epileptogenesis? Int J Physiol Pathophysiol Pharmacol 1:97–115PubMedGoogle Scholar
  26. Follesa P, Gale K, Mocchetti I (1994) Regional and temporal pattern of expression of nerve growth factor and basic fibroblast growth factor mRNA in rat brain following electroconvulsive shock. Exp Neurol 127:37–44PubMedCrossRefGoogle Scholar
  27. Fujikawa DG (2006) Neuroprotective strategies in status epilepticus. In: Wasterlain CG, Treiman DM (eds) Status epilepticus: mechanisms and management. MIT Press, Cambridge, pp 463–480Google Scholar
  28. Fujikawa DG, Itabashi HH, Wu A, Shinmei SS (2000) Status epilepticus-induced neuronal loss in humans without systemic complications or epilepsy. Epilepsia 41:981–991PubMedCrossRefGoogle Scholar
  29. Gidday JM (2006) Cerebral preconditioning and ischaemic tolerance. Nat Rev Neurosci 7:437–448PubMedCrossRefGoogle Scholar
  30. Hatazaki S, Bellver-Estelles C, Jimenez-Mateos EM, Meller R, Bonner C, Murphy N, Matsushima S, Taki W, Prehn JH, Simon RP, Henshall DC (2007) Microarray profile of seizure damage-refractory hippocampal CA3 in a mouse model of epileptic preconditioning. Neuroscience 150:467–477PubMedCrossRefGoogle Scholar
  31. Henshall DC, Simon RP (2005) Epilepsy and apoptosis pathways. J Cereb Blood Flow Metab 25:1557–1572PubMedCrossRefGoogle Scholar
  32. Henshall DC, Clark RS, Adelson PD, Chen M, Watkins SC, Simon RP (2000) Alterations in bcl-2 and caspase gene family protein expression in human temporal lobe epilepsy. Neurology 55:250–257PubMedCrossRefGoogle Scholar
  33. Henshall DC, Schindler CK, So NK, Lan JQ, Meller R, Simon RP (2004) Death-associated protein kinase expression in human temporal lobe epilepsy. Ann Neurol 55:485–494PubMedCrossRefGoogle Scholar
  34. Heurteaux C, Lauritzen I, Widmann C, Lazdunski M (1995) Essential role of adenosine, adenosine A1 receptors, and ATP-sensitive K  +  channels in cerebral ischemic preconditioning. Proc Natl Acad Sci USA 92:4666–4670PubMedCrossRefGoogle Scholar
  35. Jiang W, Van Cleemput J, Sheerin AH, Ji SP, Zhang Y, Saucier DM, Corcoran ME, Zhang X (2005) Involvement of extracellular regulated kinase and p38 kinase in hippocampal seizure tolerance. J Neurosci Res 81:581–588PubMedCrossRefGoogle Scholar
  36. Jimenez-Mateos EM, Hatazaki S, Johnson MB, Bellver-Estelles C, Mouri G, Bonner C, Prehn JH, Meller R, Simon RP, Henshall DC (2008) Hippocampal transcriptome after status epilepticus in mice rendered seizure damage-tolerant by epileptic preconditioning features suppressed ­calcium and neuronal excitability pathways. Neurobiol Dis 32:442–453PubMedCrossRefGoogle Scholar
  37. Jimenez-Mateos EM, Mouri G, Conroy RM, Henshall DC (2010) Epileptic tolerance is associated with enduring neuroprotection and uncoupling of the relationship between CA3 damage, neuropeptide Y rearrangement and spontaneous seizures following intra-amygdala kainic acid-induced status epilepticus in mice. Neuroscience 171:556–565PubMedCrossRefGoogle Scholar
  38. Kelly ME, McIntyre DC (1990) Previous kindling protects the pyriform cortex from neuronal damage during kainic acid-induced status epilepticus. Epilepsia 31:634Google Scholar
  39. Kelly ME, McIntyre DC (1991) Previous amygdala kindling protects the ipsilateral pyriform cortex but not the hippocampi from neuronal damage during kainic acid-induced status epilepticus. Epilepsia 32:40Google Scholar
  40. Kelly ME, McIntyre DC (1994) Hippocampal kindling protects several structures from the neuronal damage resulting from kainic acid-induced status epilepticus. Brain Res 634:245–256PubMedCrossRefGoogle Scholar
  41. Kondratyev A, Sahibzada N, Gale K (2001) Electroconvulsive shock exposure prevents neuronal apoptosis after kainic acid-evoked status epilepticus. Brain Res Mol Brain Res 91:1–13PubMedCrossRefGoogle Scholar
  42. Lahteinen S, Pitkanen A, Knuuttila J, Toronen P, Castren E (2004) Brain-derived neurotrophic factor signaling modifies hippocampal gene expression during epileptogenesis in transgenic mice. Eur J Neurosci 19:3245–3254PubMedCrossRefGoogle Scholar
  43. Lere C, El Bahh B, Le Gal La Salle G, Rougier A (2002) A model of ‘epileptic tolerance’ for investigating neuroprotection, epileptic susceptibility and gene expression-related plastic changes. Brain Res Brain Res Protoc 9:49–56PubMedCrossRefGoogle Scholar
  44. Li T, Quan Lan J, Fredholm BB, Simon RP, Boison D (2007) Adenosine dysfunction in astrogliosis: cause for seizure generation? Neuron Glia Biol 3:353–366PubMedCrossRefGoogle Scholar
  45. Marini AM, Paul SM (1992) N-methyl-D-aspartate receptor-mediated neuroprotection in cerebellar granule cells requires new RNA and protein synthesis. Proc Natl Acad Sci USA 89:6555–6559PubMedCrossRefGoogle Scholar
  46. Marini AM, Rabin SJ, Lipsky RH, Mocchetti I (1998) Activity-dependent release of brain-derived neurotrophic factor underlies the neuroprotective effect of N-methyl-D-aspartate. J Biol Chem 273:29394–29399PubMedCrossRefGoogle Scholar
  47. Mathern GW, Leiphart JL, De Vera A, Adelson PD, Seki T, Neder L, Leite JP (2002) Seizures decrease postnatal neurogenesis and granule cell development in the human fascia dentata. Epilepsia 43(Suppl 5):68–73PubMedCrossRefGoogle Scholar
  48. Mehler MF (2008) Epigenetics and the nervous system. Ann Neurol 64:602–617PubMedCrossRefGoogle Scholar
  49. Meldrum BS (1997) First Alfred Meyer memorial lecture. Epileptic brain damage: a consequence and a cause of seizures. Neuropathol Appl Neurobiol 23:185–201, discussion 201–182PubMedCrossRefGoogle Scholar
  50. Meldrum BS (2002) Implications for neuroprotective treatments. Prog Brain Res 135:487–495PubMedCrossRefGoogle Scholar
  51. Meller R, Minami M, Cameron JA, Impey S, Chen D, Lan JQ, Henshall DC, Simon RP (2005) CREB-mediated Bcl-2 protein expression after ischemic preconditioning. J Cereb Blood Flow Metab 25:234–246PubMedCrossRefGoogle Scholar
  52. Meller R, Cameron JA, Torrey DJ, Clayton CE, Ordonez AN, Henshall DC, Minami M, Schindler CK, Saugstad JA, Simon RP (2006) Rapid degradation of Bim by the ubiquitin-proteasome pathway mediates short-term ischemic tolerance in cultured neurons. J Biol Chem 281:7429–7436PubMedCrossRefGoogle Scholar
  53. Moncayo J, de Freitas GR, Bogousslavsky J, Altieri M, van Melle G (2000) Do transient ischemic attacks have a neuroprotective effect? Neurology 54:2089–2094PubMedCrossRefGoogle Scholar
  54. Murphy B, Dunleavy M, Shinoda S, Schindler C, Meller R, Bellver-Estelles C, Hatazaki S, Dicker P, Yamamoto A, Koegel I, Chu X, Wang W, Xiong Z, Prehn J, Simon R, Henshall D (2007) Bcl-w protects hippocampus during experimental status epilepticus. Am J Pathol 171:1258–1268PubMedCrossRefGoogle Scholar
  55. Murphy BM, Engel T, Paucard A, Hatazaki S, Mouri G, Tanaka K, Tuffy LP, Jimenez-Mateos EM, Woods I, Dunleavy M, Bonner HP, Meller R, Simon RP, Strasser A, Prehn JH, Henshall DC (2010) Contrasting patterns of Bim induction and neuroprotection in Bim-deficient mice between hippocampus and neocortex after status epilepticus. Cell Death Differ 17:459–468PubMedCrossRefGoogle Scholar
  56. Najm I, Schreiber SS, Bruce A, Tocco G, Baudry M (1992) A short episode of seizure activity protects CA3 neurons from prolonged seizure activity-induced death. Proc Soc Neurosci 18:1146Google Scholar
  57. Najm IM, Hadam J, Ckakraverty D, Mikuni N, Penrod C, Sopa C, Markarian G, Luders HO, Babb T, Baudry M (1998) A short episode of seizure activity protects from status epilepticus- induced neuronal damage in rat brain. Brain Res 810:72–75PubMedCrossRefGoogle Scholar
  58. Noe F, Pool AH, Nissinen J, Gobbi M, Bland R, Rizzi M, Balducci C, Ferraguti F, Sperk G, During MJ, Pitkanen A, Vezzani A (2008) Neuropeptide Y gene therapy decreases chronic spontaneous seizures in a rat model of temporal lobe epilepsy. Brain 131:1506–1515PubMedCrossRefGoogle Scholar
  59. Ogita K, Yoneda Y (1994) Selective potentiation of DNA binding activities of both activator protein 1 and cyclic AMP response element binding protein through in vivo activation of N-methyl-D-aspartate receptor complex in mouse brain. J Neurochem 63:525–534PubMedCrossRefGoogle Scholar
  60. Ogita K, Okuda H, Yamamoto Y, Nishiyama N, Yoneda Y (2003) In vivo neuroprotective role of NMDA receptors against kainate-induced excitotoxicity in murine hippocampal pyramidal neurons. J Neurochem 85:1336–1346PubMedCrossRefGoogle Scholar
  61. Ooi L, Wood IC (2007) Chromatin crosstalk in development and disease: lessons from REST. Nat Rev Genet 8:544–554PubMedCrossRefGoogle Scholar
  62. Penner MR, Pinaud R, Robertson HA (2001) Rapid kindling of the hippocampus protects against neural damage resulting from status epilepticus. Neuroreport 12:453–457PubMedCrossRefGoogle Scholar
  63. Pitkanen A, Lukasiuk K (2011) Mechanisms of epileptogenesis and potential treatment targets. Lancet Neurol 10:173–186PubMedCrossRefGoogle Scholar
  64. Pitkanen A, Kharatishvili I, Narkilahti S, Lukasiuk K, Nissinen J (2005) Administration of diazepam during status epilepticus reduces development and severity of epilepsy in rat. Epilepsy Res 63:27–42PubMedCrossRefGoogle Scholar
  65. Plamondon H, Blondeau N, Heurteaux C, Lazdunski M (1999) Mutually protective actions of kainic acid epileptic preconditioning and sublethal global ischemia on hippocampal neuronal death: involvement of adenosine A1 receptors and K(ATP) channels. J Cereb Blood Flow Metab 19:1296–1308PubMedCrossRefGoogle Scholar
  66. Ploski JE, Newton SS, Duman RS (2006) Electroconvulsive seizure-induced gene expression profile of the hippocampus dentate gyrus granule cell layer. J Neurochem 99:1122–1132PubMedCrossRefGoogle Scholar
  67. Rejdak K, Rejdak R, Sieklucka-Dziuba M, Stelmasiak Z, Grieb P (2001) 2-deoxyglucose enhances epileptic tolerance evoked by transient incomplete brain ischemia in mice. Epilepsy Res 43:271–278PubMedCrossRefGoogle Scholar
  68. Rosenzweig HL, Lessov NS, Henshall DC, Minami M, Simon RP, Stenzel-Poore MP (2004) Endotoxin preconditioning prevents cellular inflammatory response during ischemic neuroprotection in mice. Stroke 35:2576–2581PubMedCrossRefGoogle Scholar
  69. Sasahira M, Lowry T, Simon RP, Greenberg DA (1995) Epileptic tolerance: prior seizures protect against seizure-induced neuronal injury. Neurosci Lett 185:95–98PubMedCrossRefGoogle Scholar
  70. Savage DD, Nadler JV, McNamara JO (1984) Reduced kainic acid binding in rat hippocampal formation after limbic kindling. Brain Res 323:128–131PubMedCrossRefGoogle Scholar
  71. Schauwecker PE (2002) Complications associated with genetic background effects in models of experimental epilepsy. Prog Brain Res 135:139–148PubMedCrossRefGoogle Scholar
  72. Shimazaki K, Ishida A, Kawai N (1994) Increase in bcl-2 oncoprotein and the tolerance to ischemia-induced neuronal death in the gerbil hippocampus. Neurosci Res 20:95–99PubMedCrossRefGoogle Scholar
  73. Shimizu S, Nagayama T, Jin KL, Zhu L, Loeffert JE, Watkins SC, Graham SH, Simon RP (2001) bcl-2 Antisense treatment prevents induction of tolerance to focal ischemia in the rat brain. J Cereb Blood Flow Metab 21:233–243PubMedCrossRefGoogle Scholar
  74. Shinoda S, Schindler CK, Meller R, So NK, Araki T, Yamamoto A, Lan JQ, Taki W, Simon RP, Henshall DC (2004) Bim regulation may determine hippocampal vulnerability after injurious seizures and in temporal lobe epilepsy. J Clin Invest 113:1059–1068PubMedGoogle Scholar
  75. Sieklucka M, Bortolotto Z, Heim C, Block F, Sontag KH (1991) Decreased susceptibility to seizures induced by bicuculline after transient bilateral clamping of the carotid arteries in rats. J Neural Transm Gen Sect 83:127–137PubMedCrossRefGoogle Scholar
  76. Sieklucka M, Heim C, Block F, Sontag KH (1992) Transient reduction of cerebral blood flow leads to longlasting increase in GABA content in vulnerable structures and decreased susceptibility to bicuculline induced seizures. J Neural Transm Gen Sect 88:87–94PubMedCrossRefGoogle Scholar
  77. Sloviter RS (1987) Decreased hippocampal inhibition and a selective loss of interneurons in experimental epilepsy. Science 235:73–76PubMedCrossRefGoogle Scholar
  78. Sloviter RS (2008) Hippocampal epileptogenesis in animal models of mesial temporal lobe epilepsy with hippocampal sclerosis: the importance of the “latent period” and other concepts. Epilepsia 49(Suppl 9):85–92PubMedCrossRefGoogle Scholar
  79. Spencer EM, Chandler KE, Haddley K, Howard MR, Hughes D, Belyaev ND, Coulson JM, Stewart JP, Buckley NJ, Kipar A, Walker MC, Quinn JP (2006) Regulation and role of REST and REST4 variants in modulation of gene expression in in vivo and in vitro in epilepsy models. Neurobiol Dis 24:41–52PubMedCrossRefGoogle Scholar
  80. Stapels M, Piper C, Yang T, Li M, Stowell C, Xiong ZG, Saugstad J, Simon RP, Geromanos S, Langridge J, Lan JQ, Zhou A (2010) Polycomb group proteins as epigenetic mediators of neuroprotection in ischemic tolerance. Sci Signal 3:ra15PubMedCrossRefGoogle Scholar
  81. Stenzel-Poore MP, Stevens SL, Xiong Z, Lessov NS, Harrington CA, Mori M, Meller R, Rosenzweig HL, Tobar E, Shaw TE, Chu X, Simon RP (2003) Effect of ischaemic preconditioning on genomic response to cerebral ischaemia: similarity to neuroprotective strategies in hibernation and hypoxia-tolerant states. Lancet 362:1028–1037PubMedCrossRefGoogle Scholar
  82. Stenzel-Poore MP, Stevens SL, King JS, Simon RP (2007) Preconditioning reprograms the response to ischemic injury and primes the emergence of unique endogenous neuroprotective phenotypes: a speculative synthesis. Stroke 38:680–685PubMedCrossRefGoogle Scholar
  83. Tanaka K, Jimenez-Mateos EM, Matsushima S, Taki W, Henshall DC (2010) Hippocampal damage after intra-amygdala kainic acid-induced status epilepticus and seizure preconditioning-mediated neuroprotection in SJL mice. Epilepsy Res 88:151–161PubMedCrossRefGoogle Scholar
  84. Tandon P, Yang Y, Das K, Holmes GL, Stafstrom CE (1999) Neuroprotective effects of brain-derived neurotrophic factor in seizures during development. Neuroscience 91:293–303PubMedCrossRefGoogle Scholar
  85. Tasaki K, Ruetzler CA, Ohtsuki T, Martin D, Nawashiro H, Hallenbeck JM (1997) Lipopolysaccharide pre-treatment induces resistance against subsequent focal cerebral ischemic damage in spontaneously hypertensive rats. Brain Res 748:267–270PubMedCrossRefGoogle Scholar
  86. Thompson JL, Bryan M, Bates T, Holmes GL (1988) Failure of kindling to alter susceptibility to kainic acid. Brain Res 466:149–151PubMedGoogle Scholar
  87. Towfighi J, Housman C, Mauger D, Vannucci RC (1999) Effect of seizures on cerebral hypoxic-ischemic lesions in immature rats. Brain Res Dev Brain Res 113:83–95PubMedGoogle Scholar
  88. Tsuchiya D, Hong S, Matsumori Y, Kayama T, Swanson RA, Dillman WH, Liu J, Panter SS, Weinstein PR (2003) Overexpression of rat heat shock protein 70 reduces neuronal injury after transient focal ischemia, transient global ischemia, or kainic acid-induced seizures. Neurosurgery 53:1179–1187, discussion 1187–1178PubMedCrossRefGoogle Scholar
  89. Vezzani A, Michalkiewicz M, Michalkiewicz T, Moneta D, Ravizza T, Richichi C, Aliprandi M, Mule F, Pirona L, Gobbi M, Schwarzer C, Sperk G (2002) Seizure susceptibility and epileptogenesis are decreased in transgenic rats overexpressing neuropeptide Y. Neuroscience 110:237–243PubMedCrossRefGoogle Scholar
  90. Wasterlain CG, Fujikawa DG, Penix L, Sankar R (1993) Pathophysiological mechanisms of brain damage from status epilepticus. Epilepsia 34:S37–S53PubMedCrossRefGoogle Scholar
  91. Xu B, McIntyre DC, Fahnestock M, Racine RJ (2004) Strain differences affect the induction of status epilepticus and seizure-induced morphological changes. Eur J Neurosci 20:403–418PubMedCrossRefGoogle Scholar
  92. Yenari MA, Fink SL, Sun GH, Chang LK, Patel MK, Kunis DM, Onley D, Ho DY, Sapolsky RM, Steinberg GK (1998) Gene therapy with HSP72 is neuroprotective in rat models of stroke and epilepsy. Ann Neurol 44:584–591PubMedCrossRefGoogle Scholar
  93. Yoneda Y, Ogita K (1994) Rapid and selective enhancement of DNA binding activity of the transcription factor AP1 by systemic administration of N-methyl-D-aspartate in murine hippocampus. Neurochem Int 25:263–271PubMedCrossRefGoogle Scholar
  94. Zukin RS (2010) Eradicating the mediators of neuronal death with a fine-tooth comb. Sci Signal 3:pe20PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Physiology & Medical PhysicsRoyal College of Surgeons in IrelandDublin 2Ireland

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