Skip to main content

What Is the Clinical Relevance of In Vitro Epileptiform Activity?

  • Chapter
  • First Online:
Issues in Clinical Epileptology: A View from the Bench

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 813))

Abstract

In vitro preparations provide an exceptionally rapid, flexible, and accessible approach to long-standing problems in epilepsy research including ictogenesis, epileptogenesis, and drug resistance. Acute slices suffer from a reduction in network connectivity that has traditionally been compensated through the application of acute convulsants. The utility and limitations of this approach have become clear over time and are discussed here. Other approaches such as organotypic slice preparations demonstrate the full spectrum of spontaneous epileptic activity and more closely mimic human responses to anticonvulsants, including the development of drug resistance. Newly developed transgenic and vector expression systems for fluorophores, optogenetics, and orphan receptors are being coupled with advances in imaging and image analysis. These developments have created the capacity to rapidly explore many new avenues of epilepsy research such as vascular, astrocytic and mitochondrial contributions to epileptogenesis. Rigorous study design as well as close collaboration with in vivo laboratories and clinical investigators will accelerate the translation of the exciting discoveries that will be revealed by these new techniques.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Notes

  1. 1.

    http://www.nc3rs.org.uk

References

  1. Achilles K, Okabe A, Ikeda M, Shimizu-Okabe C, Yamada J, Fukuda A, Luhmann HJ, Kilb W (2007) Kinetic properties of Cl uptake mediated by Na+− dependent K+−2Cl cotransport in immature rat neocortical neurons. J Neurosci 27:8616–8627

    Article  CAS  PubMed  Google Scholar 

  2. Albus K, Heinemann U, Kovacs R (2013) Network activity in hippocampal slice cultures revealed by long-term in vitro recordings. J Neurosci Methods 217:1–8

    Article  PubMed  Google Scholar 

  3. Albus K, Wahab A, Heinemann U (2008) Standard antiepileptic drugs fail to block epileptiform activity in rat organotypic hippocampal slice cultures. Br J Pharmacol 154:709–724

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Albus K, Wahab A, Heinemann U (2012) Primary afterdischarge in organotypic hippocampal slice cultures: effects of standard antiepileptic drugs. Epilepsia 53:1928–1936

    Article  CAS  PubMed  Google Scholar 

  5. Avoli M, Louvel J, Mattia D, Olivier A, Esposito V, Pumain R, D’Antuono M (2003) Epileptiform synchronization in the human dysplastic cortex. Epileptic Disord 5(Suppl 2):S45–S50

    PubMed  Google Scholar 

  6. Baldino F Jr, Wolfson B, Heinemann U, Gutnick MJ (1986) An N-methyl-D-aspartate (NMDA) receptor antagonist reduces bicuculline-induced depolarization shifts in neocortical explant cultures. Neurosci Lett 70:101–105

    Article  CAS  PubMed  Google Scholar 

  7. Barbarosie M, Avoli M (1997) CA3-driven hippocampal-entorhinal loop controls rather than sustains in vitro limbic seizures. J Neurosci 17:9308–9314

    CAS  PubMed  Google Scholar 

  8. Berdichevsky Y, Dryer AM, Saponjian Y, Mahoney MM, Pimentel CA, Lucini CA, Usenovic M, Staley KJ (2013) PI3K-Akt signaling activates mTOR-mediated epileptogenesis in organotypic hippocampal culture model of post-traumatic epilepsy. J Neurosci 33:9056–9067

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Berdichevsky Y, Dzhala V, Mail M, Staley KJ (2012) Interictal spikes, seizures and ictal cell death are not necessary for post-traumatic epileptogenesis in vitro. Neurobiol Dis 45:774–785

    Article  PubMed Central  PubMed  Google Scholar 

  10. Berdichevsky Y, Sabolek H, Levine JB, Staley KJ, Yarmush ML (2009) Microfluidics and multielectrode array-compatible organotypic slice culture method. J Neurosci Methods 178:59–64

    Article  PubMed Central  PubMed  Google Scholar 

  11. Bittner K, Müller W (1999) Oxidative downmodulation of the transient K-current I A by intracellular arachidonic acid in rat hippocampal neurons. J Neurophysiol 81:508–511

    Google Scholar 

  12. Boehlen A, Schwake M, Dost R, Kunert A, Fidzinski P, Heinemann U, Gebhardt C (2013) The new KCNQ2 activator 4-Chlor-N-(6-chlor-pyridin-3-yl)-benzamid displays anticonvulsant potential. Br J Pharmacol 168:1182–1200

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Bogaerts V, Theuns J, van Broeckhoven C (2008) Genetic findings in Parkinson’s disease and translation into treatment: a leading role for mitochondria? Genes Brain Behav 7:129–151

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Brückner C, Heinemann U (2000) Effects of standard anticonvulsant drugs on different patterns of epileptiform discharges induced by 4-aminopyridine in combined entorhinal cortex-hippocampal slices. Brain Res 859:15–20

    Article  PubMed  Google Scholar 

  15. Brückner C, Stenkamp K, Meierkord H, Heinemann U (1999) Epileptiform discharges induced by combined application of bicucculline and 4-aminopyridine are resistant to standard anticonvulsants in slices of rats. Neurosci Lett 268:163–165

    Article  PubMed  Google Scholar 

  16. Cacheaux LP, Ivens S, David Y, Lakhter AJ, Bar-Klein G, Shapira M, Heinemann U, Friedman A, Kaufer D (2009) Transcriptome profiling reveals TGF-beta signaling involvement in epileptogenesis. J Neurosci 29:8927–8935

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Cock H (2007) The role of mitochondria in status epilepticus. Epilepsia 48:24–27

    Article  CAS  PubMed  Google Scholar 

  18. De Lanerolle NC, Gunel M, Sundaresan S, Shen MY, Brines ML, Spencer DD (1995) Vasoactive intestinal polypeptide and its receptor changes in human temporal lobe epilepsy. Brain Res 686:182–193

    Article  PubMed  Google Scholar 

  19. de Curtis M, Pare D (2004) The rhinal cortices: a wall of inhibition between the neocortex and the hippocampus. Prog Neurobiol 74:101–110

    Article  PubMed  Google Scholar 

  20. DeFelipe J, Sola RG, Marco P (1996) Changes in excitatory and inhibitory synaptic circuits in the human epileptogenic neocortex. In: Conti F, Hicks TP (eds) Excitatory amino acids and the cerebral cortex. MIT Press, Cambridge, MA, pp 299–312

    Google Scholar 

  21. Dietzel I, Heinemann U, Hofmeier G, Lux HD (1980) Transient changes in the size of the extracellular space in the sensorimotor cortex of cats in relation to stimulus induced changes in potassium concentration. Exp Brain Res 40:432–439

    Article  CAS  PubMed  Google Scholar 

  22. Dreier JP, Major S, Pannek HW, Woitzik J, Scheel M, Wiesenthal D, Martus P, Winkler MK, Hartings JA, Fabricius M, Speckmann EJ, Gorji A (2012) Spreading convulsions, spreading depolarization and epileptogenesis in human cerebral cortex. Brain 135:259–275

    Article  PubMed Central  PubMed  Google Scholar 

  23. Dreier JP, Zhang CL, Heinemann U (1998) Phenytoin, phenobarbital, and midazolam fail to stop status epilepticus-like activity induced by low magnesium in rat entorhinal slices, but can prevent its development. Acta Neurol Scand 98:154–160

    Article  CAS  PubMed  Google Scholar 

  24. Duley L, Gulmezoglu AM, Henderson-Smart DJ, Chou D (2010) Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane Database Syst Rev 11, CD000025

    PubMed  Google Scholar 

  25. Dyhrfjeld-Johnsen J, Berdichevsky Y, Swiercz W, Sabolek H, Staley KJ (2010) Interictal spikes precede ictal discharges in an organotypic hippocampal slice culture model of epileptogenesis. J Clin Neurophysiol 27:418–424

    Article  CAS  PubMed  Google Scholar 

  26. Dzhala VI, Brumback AC, Staley KJ (2008) Bumetanide enhances phenobarbital efficacy in a neonatal seizure model. Ann Neurol 63:222–235

    Article  CAS  PubMed  Google Scholar 

  27. Dzhala VI, Kuchibhotla KV, Glykys JC, Kahle KT, Swiercz WB, Feng G, Kuner T, Augustine GJ, Bacskai BJ, Staley KJ (2010) Progressive NKCC1-dependent neuronal chloride accumulation during neonatal seizures. J Neurosci 30:11745–11761

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Dzhala VI, Talos DM, Sdrulla DA, Brumback AC, Mathews GC, Benke TA, Delpire E, Jensen FE, Staley KJ (2005) NKCC1 transporter facilitates seizures in the developing brain. Nat Med 11:1205–1213

    Article  CAS  PubMed  Google Scholar 

  29. Eid T, Thomas MJ, Spencer DD, Runden-Pran E, Lai JCK, Malthankar GV, Kim JH, Danbolt NC, Ottersen OP, De Lanerolle NC (2004) Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy. Lancet 363:28–37

    Article  CAS  PubMed  Google Scholar 

  30. Gabriel S, Njunting M, Pomper JK, Merschhemke M, Sanabria ERG, Eilers A, Kivi A, Zeller M, Meencke HJ, Cavalheiro EA, Heinemann U, Lehmann TN (2004) Stimulus and potassium-induced epileptiform activity in the human dentate gyrus from patients with and without hippocampal sclerosis. J Neurosci 24:10416–10430

    Article  CAS  PubMed  Google Scholar 

  31. Gloveli T, Albrecht D, Heinemann U (1995) Properties of low Mg2+ induced epileptiform activity in rat hippocampal and entorhinal cortex slices during adolescence. Dev Brain Res 87:145–152

    Article  CAS  Google Scholar 

  32. Graulich J, Hoffmann U, Maier RF, Ruscher K, Pomper JK, Ko HK, Gabriel S, Obladen M, Heinemann U (2002) Acute neuronal injury after hypoxia is influenced by the reoxygenation mode in juvenile hippocampal slice cultures. Brain Res Dev Brain Res 137:35–42

    Article  CAS  PubMed  Google Scholar 

  33. Griffiths T, Evans MC, Meldrum BS (1982) Intracellular sites of early calcium accumulation in the rat hippocampus during status epilepticus. Neurosci Lett 30:329–334

    Article  CAS  PubMed  Google Scholar 

  34. Gutierrez R, Heinemann U (1999) Synaptic reorganization in explanted cultures of rat hippocampus. Brain Res 815:304–316

    Article  CAS  PubMed  Google Scholar 

  35. Gutierrez R, Heinemann U (2001) Kindling induces transient fast inhibition in the dentate gyrus–CA3 projection. Eur J Neurosci 13:1371–1379

    Article  CAS  PubMed  Google Scholar 

  36. Haas HL, Jefferys JGR (1984) Low-calcium field burst discharges of CA1 pyramidal neurones in rat hippocampal slices. J Physiol Lond 354:185–201

    CAS  PubMed Central  PubMed  Google Scholar 

  37. Hablitz JJ, Heinemann U, Lux HD (1986) Step reductions in extracellular Ca2+ activate a transient inward current in chick dorsal root ganglion cells. Biophys J 50:753–757

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Hablitz JJ, Heinemann U, Weiss DS (1984) Epileptiform activity and spreading depression in the neocortical slice. Epilepsia 25:670

    Google Scholar 

  39. Huberfeld G, Menendez dP, Pallud J, Cohen I, Le Van Quyen M, Adam C, Clemenceau S, Baulac M, Miles R (2011) Glutamatergic pre-ictal discharges emerge at the transition to seizure in human epilepsy. Nat Neurosci 14:627–634; 2

    Article  CAS  PubMed  Google Scholar 

  40. Ivens S, Kaufer D, Flores LP, Bechmann I, Zumsteg D, Tomkins O, Seiffert E, Heinemann U, Friedman A (2007) TGF-beta receptor-mediated albumin uptake into astrocytes is involved in neocortical epileptogenesis. Brain 130:535–547

    Article  PubMed  Google Scholar 

  41. Jandova K, Pasler D, Antonio LL, Raue C, Ji S, Njunting M, Kann O, Kovacs R, Meencke HJ, Cavalheiro EA, Heinemann U, Gabriel S, Lehmann TN (2006) Carbamazepine-resistance in the epileptic dentate gyrus of human hippocampal slices. Brain 129:3290–3306

    Article  PubMed  Google Scholar 

  42. Jauch R, Windmüller O, Lehmann TN, Heinemann U, Gabriel S (2002) Effects of barium, furosemide, ouabaine and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) on ionophoretically-induced changes in extracellular potassium concentration in hippocampal slices from rats and from patients with epilepsy. Brain Res 925:18–27

    Article  CAS  PubMed  Google Scholar 

  43. Jefferys JGR, Haas HL (1982) Synchronized bursting of CA1 hippocampal pyramidal cells in the absence of synaptic transmission. Nature 300:448–450

    Article  CAS  PubMed  Google Scholar 

  44. Jiang J, Quan Y, Ganesh T, Pouliot WA, Dudek FE, Dingledine R (2013) Inhibition of the prostaglandin receptor EP2 following status epilepticus reduces delayed mortality and brain inflammation. Proc Natl Acad Sci U S A 110:3591–3596

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Johnston D, Brown TH (1981) Giant synaptic potential hypothesis for epileptiform activity. Science 211:294–297

    Article  CAS  PubMed  Google Scholar 

  46. Jungehulsing GJ, Heuschmann PU, Holtkamp M, Schwab S, Kolominsky-Rabas PL (2013) Incidence and predictors of post-stroke epilepsy. Acta Neurol Scand 127:427–430

    Article  PubMed  Google Scholar 

  47. Kahle KT, Barnett SM, Sassower KC, Staley KJ (2009) Decreased seizure activity in a human neonate treated with bumetanide, an inhibitor of the Na(+)-K(+)-2Cl(−) cotransporter NKCC1. J Child Neurol 24:572–576

    Article  PubMed  Google Scholar 

  48. Kann O, Kovacs R, Njunting M, Behrens CJ, Otahal J, Lehmann TN, Gabriel S, Heinemann U (2005) Metabolic dysfunction during neuronal activation in the ex vivo hippocampus from chronic epileptic rats and humans. Brain 128:2396–2407

    Article  PubMed  Google Scholar 

  49. Khalilov I, Holmes GL, Ben-Ari Y (2003) In vitro formation of a secondary epileptogenic mirror focus by interhippocampal propagation of seizures. Nat Neurosci 6:1079–1085

    Article  CAS  PubMed  Google Scholar 

  50. Khurgel M, Switzer RC III, Teskey GC, Spiller AE, Racine RJ, Ivy GO (1995) Activation of astrocytes during epileptogenesis in the absence of neuronal degeneration. Neurobiol Dis 2:23–35

    Article  CAS  PubMed  Google Scholar 

  51. Köhling R, Lücke A, Straub H, Speckmann E-J, Tuxhorn I, Wolf P, Pannek H, Oppel F (1998) Spontaneous sharp waves in human neocortical slices excised from epileptic patients. Brain 121:1073–1087

    Article  PubMed  Google Scholar 

  52. Konnerth A, Heinemann U, Yaari Y (1984) Slow transmission of neural activity in hippocampal area CA1 in the absence of active chemical synapses. Nature 307:69–71

    Article  CAS  PubMed  Google Scholar 

  53. Kovacs R, Heinemann U, Steinhauser C (2012) Mechanisms underlying blood-brain barrier dysfunction in brain pathology and epileptogenesis: role of astroglia. Epilepsia 53(Suppl 6):53–59

    Article  CAS  PubMed  Google Scholar 

  54. Kovacs R, Schuchmann S, Gabriel S, Kann O, Kardos J, Heinemann U (2002) Free radical-mediated cell damage after experimental status epilepticus in hippocampal slice cultures. J Neurophysiol 88:2909–2918

    Article  CAS  PubMed  Google Scholar 

  55. Lapilover EG, Lippmann K, Salar S, Maslarova A, Dreier JP, Heinemann U, Friedman A (2012) Peri-infarct blood-brain barrier dysfunction facilitates induction of spreading depolarization associated with epileptiform discharges. Neurobiol Dis 48:495–506

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Lehmann TN, Gabriel S, Eilers A, Njunting M, Kovacs R, Schulze K, Lanksch WR, Heinemann U (2001) Fluorescent tracer in pilocarpine-treated rats shows widespread aberrant hippocampal neuronal connectivity. Eur J Neurosci 14:83–95

    Article  CAS  PubMed  Google Scholar 

  57. Leschinger A, Stabel J, Igelmund P, Heinemann U (1993) Pharmacological and electrographic properties of epileptiform activity induced by elevated K+ and lowered Ca2+ and Mg2+ concentration in rat hippocampal slices. Exp Brain Res 96:230–240

    Article  CAS  PubMed  Google Scholar 

  58. Leutgeb JK, Frey JU, Behnisch T (2003) LTP in cultured hippocampal-entorhinal cortex slices from young adult (P25-30) rats. J Neurosci Methods 130:19–32

    Article  PubMed  Google Scholar 

  59. Liotta A, Caliskan G, Ul HR, Hollnagel JO, Rosler A, Heinemann U, Behrens CJ (2011) Partial disinhibition is required for transition of stimulus-induced sharp wave-ripple complexes into recurrent epileptiform discharges in rat hippocampal slices. J Neurophysiol 105:172–187

    Article  CAS  PubMed  Google Scholar 

  60. Lücke A, Nagao T, Köhling R, Avoli M (1995) Synchronous potentials and elevations in [K+]O in the adult rat entorhinal cortex maintained in vitro. Neurosci Lett 185:155–158

    Article  PubMed  Google Scholar 

  61. Luhmann HJ, Dzhala VI, Ben Ari Y (2000) Generation and propagation of 4-AP-induced epileptiform activity in neonatal intact limbic structures in vitro. Eur J Neurosci 12:2757–2768

    Article  CAS  PubMed  Google Scholar 

  62. MacDonald JF, Xiong ZG, Jackson MF (2006) Paradox of Ca2+ signaling, cell death and stroke. Trends Neurosci 29:75–81

    Article  CAS  PubMed  Google Scholar 

  63. Meier JC, Henneberger C, Melnick I, Racca C, Harvey RJ, Heinemann U, Schmieden V, Grantyn R (2005) RNA editing produces glycine receptor alpha3(P185L), resulting in high agonist potency. Nat Neurosci 8:736–744

    Article  CAS  PubMed  Google Scholar 

  64. Morin-Brureau M, Rigau V, Lerner-Natoli M (2012) Why and how to target angiogenesis in focal epilepsies. Epilepsia 53(Suppl 6):64–68

    Article  CAS  PubMed  Google Scholar 

  65. Okazaki MM, Evenson DA, Nadler JV (1995) Hippocampal mossy fiber sprouting and synapse formation after status epilepticus in rats: Visualization after retrograde transport of biocytin. J Comp Neurol 352:515–534

    Article  CAS  PubMed  Google Scholar 

  66. Papageorgiou IE, Gabriel S, Fetani AF, Kann O, Heinemann U (2011) Redistribution of astrocytic glutamine synthetase in the hippocampus of chronic epileptic rats. Glia 59:1706–1718

    Article  PubMed  Google Scholar 

  67. Pfeiffer M, Draguhn A, Meierkord H, Heinemann U (1996) Effects of γ-aminobutyric acid (GABA) agonists and GABA uptake inhibitors on pharmacosensitive and pharmacoresistant epileptiform activity in vitro. Br J Pharmacol 119:569–577

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. Pomper JK, Haack S, Petzold GC, Buchheim K, Gabriel S, Hoffmann U, Heinemann U (2006) Repetitive spreading depression-like events result in cell damage in juvenile hippocampal slice cultures maintained in normoxia. J Neurophysiol 95:355–368

    Article  PubMed  Google Scholar 

  69. Pumain R, Menini C, Heinemann U, Silva-Barrat C, Louvel J (1985) Chemical synaptic transmission is not necessary for epileptic activity to persist in the neocortex of the photosensitive baboon. Exp Neurol 89:250–258

    Article  CAS  PubMed  Google Scholar 

  70. Quilichini PP, Diabira D, Chiron C, Milh M, Ben-Ari Y, Gozlan H (2003) Effects of antiepileptic drugs on refractory seizures in the intact immature corticohippocampal formation in vitro. Epilepsia 44:1365–1374

    Article  CAS  PubMed  Google Scholar 

  71. Rector DM, Burk P, Harper RM (1993) A data acquisition system for long-term monitoring of physiological and video signals. Electroencephalogr Clin Neurophysiol 87:380–384

    Article  CAS  PubMed  Google Scholar 

  72. Rigau V, Morin M, Rousset MC, de Bock F, Lebrun A, Coubes P, Picot MC, Baldy-Moulinier M, Bockaert J, Crespel A, Lerner-Natoli M (2007) Angiogenesis is associated with blood-brain barrier permeability in temporal lobe epilepsy. Brain 130:1942–1956

    Article  PubMed  Google Scholar 

  73. Rocha L, Engel J Jr, Ackermann RF (1991) Effects of chronic naloxone pretreatment on amygdaloid kindling in rats. Epilepsy Res 10:103–110

    Article  CAS  PubMed  Google Scholar 

  74. Scheffer IE, Berkovic SF (2003) The genetics of human epilepsy. Trends Pharmacol Sci 24:428–433

    Article  CAS  PubMed  Google Scholar 

  75. Schmitt FC, Buchheim K, Meierkord H, Holtkamp M (2006) Anticonvulsant properties of hypothermia in experimental status epilepticus. Neurobiol Dis 23:689–696

    Article  CAS  PubMed  Google Scholar 

  76. Schuchmann S, Müller W, Heinemann U (1998) Altered Ca2+-signaling and mitochondrial deficiencies in hippocampal neurons of trisomy 16 mice: a model of Down’s syndrome. J Neurosci 18:7216–7231

    CAS  PubMed  Google Scholar 

  77. Schwartzkroin PA, Prince DA (1977) Penicillin-induced epileptiform activity in the hippocampal in vitro preparation. Ann Neurol 1:463–469

    Article  CAS  PubMed  Google Scholar 

  78. Schwartzkroin PA, Prince DA (1978) Cellular and field potential properties of epileptogenic hippocampal slices. Brain Res 147:117–130

    Article  CAS  PubMed  Google Scholar 

  79. Seiffert E, Dreier JP, Ivens S, Bechmann I, Tomkins O, Heinemann U, Friedman A (2004) Lasting blood-brain barrier disruption induces epileptic focus in the rat somatosensory cortex. J Neurosci 24:7829–7836

    Article  CAS  PubMed  Google Scholar 

  80. Somjen GG, Kager H, Wadman WJ (2009) Calcium sensitive non-selective cation current promotes seizure-like discharges and spreading depression in a model neuron. J Comput Neurosci 26:139–147

    Article  CAS  PubMed  Google Scholar 

  81. Spencer SS, Spencer DD (1994) Entorhinal-hippocampal interactions in medial temporal lobe epilepsy. Epilepsia 35:721–727

    Article  CAS  PubMed  Google Scholar 

  82. Streit AK, Derst C, Wegner S, Heinemann U, Zahn RK, Decher N (2011) RNA editing of Kv1.1 channels may account for reduced ictogenic potential of 4-aminopyridine in chronic epileptic rats. Epilepsia 52:645–648

    Article  CAS  PubMed  Google Scholar 

  83. Swartzwelder HS, Lewis DV, Anderson WW, Wilson WA (1987) Seizure-like events in brain slices: suppression by interictal activity. Brain Res 410:362–366

    Article  CAS  PubMed  Google Scholar 

  84. Swiercz W, Cios K, Hellier J, Yee A, Staley K (2007) Effects of synaptic depression and recovery on synchronous network activity. J Clin Neurophysiol 24:165–174

    Article  PubMed  Google Scholar 

  85. Thompson SM, Gähwiler BH (1989) Activity-dependent disinhibition. II. Effects of extracellular potassium, furosemide, and membrane potential on E Cl in hippocampal CA3 neurons. J Neurophysiol 61:512–523

    CAS  PubMed  Google Scholar 

  86. Tomkins O, Shelef I, Kaizerman I, Misk A, Afawi Z, Eliushin A, Gidon M, Cohen A, Zumsteg D, Friedman A (2007) Blood-brain barrier disruption in post-traumatic epilepsy. J Neurol Neurosurg Psychiatry 79:774–777

    Article  PubMed  Google Scholar 

  87. Traynelis SF, Dingledine R (1988) Potassium-induced spontaneous electrographic seizures in the rat hippocampal slice. J Neurophysiol 59:259–276

    CAS  PubMed  Google Scholar 

  88. Verret L, Mann EO, Hang GB, Barth AM, Cobos I, Ho K, Devidze N, Masliah E, Kreitzer AC, Mody I, Mucke L, Palop JJ (2012) Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. Cell 149:708–721

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  89. Vezzani A (2008) Innate immunity and inflammation in temporal lobe epilepsy: new emphasis on the role of complement activation. Epilepsy Curr 8:75–77

    Article  PubMed Central  PubMed  Google Scholar 

  90. Walther H, Lambert JDC, Jones RSG, Heinemann U, Hamon B (1986) Epileptiform activity in combined slices of the hippocampus, subiculum and entorhinal cortex during perfusion with low magnesium medium. Neurosci Lett 69:156–161

    Article  CAS  PubMed  Google Scholar 

  91. Wei WL, Sun HS, Olah ME, Sun X, Czerwinska E, Czerwinski W, Mori Y, Orser BA, Xiong ZG, Jackson MF, Tymianski M, MacDonald JF (2007) TRPM7 channels in hippocampal neurons detect levels of extracellular divalent cations. Proc Natl Acad Sci U S A 104:16323–16328

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  92. Winkler MK, Chassidim Y, Lublinsky S, Revankar GS, Major S, Kang EJ, Oliveira-Ferreira AI, Woitzik J, Sandow N, Scheel M, Friedman A, Dreier JP (2012) Impaired neurovascular coupling to ictal epileptic activity and spreading depolarization in a patient with subarachnoid hemorrhage: possible link to blood-brain barrier dysfunction. Epilepsia 53(Suppl 6):22–30

    Article  PubMed Central  PubMed  Google Scholar 

  93. Yamamoto C, Kawai N (1967) Seizure discharge evoked in vitro in thin sections from guinea pig hippocampus. Science 155:341–342

    Article  CAS  PubMed  Google Scholar 

  94. Yee AS, Longacher JM, Staley KJ (2003) Convulsant and anticonvulsant effects on spontaneous CA3 population bursts. J Neurophysiol 89:427–441

    Article  PubMed  Google Scholar 

  95. Yu FH, Mantegazza M, Westenbroek RE, Robbins CA, Kalume F, Burton KA, Spain WJ, McKnight GS, Scheuer T, Catterall WA (2006) Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy. Nat Neurosci 9:1142–1149

    Article  CAS  PubMed  Google Scholar 

  96. Yu W, Jegla T, Wagoner K, Wickenden AD (2000) Retigabine, a novel anti-convulsant, enhances activation of KCNQ27Q3 potassium channels. Mol Pharmacol 58:591–600

    PubMed  Google Scholar 

  97. Yus-Najera E, Munoz A, Salvador N, Jensen BS, Rasmussen HB, DeFelipe J, Villarroel A (2003) Localization of KCNQ5 in the normal and epileptic human temporal neocortex and hippocampal formation. Neuroscience 120:353–364

    Article  CAS  PubMed  Google Scholar 

  98. Zahn RK, Tolner EA, Derst C, Gruber C, Veh RW, Heinemann U (2008) Reduced ictogenic potential of 4-aminopyridine in the perirhinal and entorhinal cortex of kainate-treated chronic epileptic rats. Neurobiol Dis 29:186–200

    Article  CAS  PubMed  Google Scholar 

  99. Zhang CL, Dreier JP, Heinemann U (1995) Paroxysmal epileptiform discharges in temporal lobe slices after prolonged exposure to low magnesium are resistant to clinically used anticonvulsants. Epilepsy Res 20:105–111

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgement

UH is funded by DFG EXC Neurocure

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kevin J. Staley .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Heinemann, U., Staley, K.J. (2014). What Is the Clinical Relevance of In Vitro Epileptiform Activity?. In: Scharfman, H., Buckmaster, P. (eds) Issues in Clinical Epileptology: A View from the Bench. Advances in Experimental Medicine and Biology, vol 813. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8914-1_2

Download citation

  • DOI: https://doi.org/10.1007/978-94-017-8914-1_2

  • Published:

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-017-8913-4

  • Online ISBN: 978-94-017-8914-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics