Pathophysiology of Status Epilepticus: Experimental Data

  • Uwe Heinemann
  • Martin Holtkamp
Reference work entry

Introduction and Definitions

Some 150 years ago, Armand Trousseau from Paris recognized that during “status epilepticus, something happens [in the brain] that requires an explanation” (Trousseau 1868). In spite of recent progress, treatment success is still limited, since more than 30% of patients develop refractory status epilepticus (SE) that is often associated with severe neuronal and clinical sequelae. There is a long-lasting debate on how long seizure activity should last to define SE (Chen and Wasterlain 2006). While in epidemiological studies, the definition of SE is commonly based on a minimal seizure duration of 30 min (Wasterlain and Chen 2006), in clinical practice, anticonvulsant treatment should be initiated in both generalized convulsive and non-convulsive forms of SE 5 min after onset of seizure activity (Chen and Wasterlain 2006; Meierkord and Holtkamp 2007). However, in some conditions, even shorter periods of seizure activity can result in neuronal damage. To better...


Status Epilepticus GABAA Receptor Slice Culture Refractory Status Epilepticus Radical Oxygen Species 
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.

List of Abbreviations


Antiepileptic drug


α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid


Blood brain barrier


γ-Amino-butyric acid




Radical oxygen species


Reactive oxygen species


Status epilepticus


Self-sustaining status epilepticus


Transforming growth factor β receptor


  1. Brandt C, Glien M, Potschka H, Volk H, Loscher W (2003) Epileptogenesis and neuropathology after different types of status epilepticus induced by prolonged electrical stimulation of the basolateral amygdala in rats. Epilepsy Res 55:83–103CrossRefPubMedGoogle Scholar
  2. Chen JW, Wasterlain CG (2006) Status epilepticus: pathophysiology and management in adults. Lancet Neurol 5:246–256CrossRefPubMedGoogle Scholar
  3. Cole AJ, Koh S, Zheng Y (2002) Are seizures harmful: what can we learn from animal models? Prog Brain Res 135:13–23CrossRefPubMedGoogle Scholar
  4. Dietzel I, Heinemann U, Lux HD (1989) Relations between slow extracellular potential changes, glial potassium buffering, and electrolyte and cellular volume changes during neuronal hyperactivity in cat brain. Glia 2:25–44CrossRefPubMedGoogle Scholar
  5. Heinemann U, Konnerth A, Pumain R, Wadman WJ (1986) Extracellular calcium and potassium concentration changes in chronic epileptic brain tissue. Adv Neurol 44:641–661PubMedGoogle Scholar
  6. Heinemann U, Buchheim K, Gabriel S, Kann O, Kovacs R, Schuchmann S (2002a) Cell death and metabolic activity during epileptiform discharges and status epilepticus in the hippocampus. Prog Brain Res 135:197–210CrossRefPubMedGoogle Scholar
  7. Heinemann U, Buchheim K, Gabriel S, Kann O, Kovacs R, Schuchmann S (2002b) Coupling of electrical and metabolic activity during epileptiform discharges. Epilepsia 43(Suppl 5):168–173CrossRefPubMedGoogle Scholar
  8. Holtkamp M, Meierkord H (2007) Anticonvulsant, antiepileptogenic, and antiictogenic pharmacostrategies. Cell Mol Life Sci 64:2023–2041CrossRefPubMedGoogle Scholar
  9. Holtkamp M, Matzen J, van Landeghem F, Buchheim K, Meierkord H (2005) Transient loss of inhibition precedes spontaneous seizures after experimental status epilepticus. Neurobiol Dis 19:162–170CrossRefPubMedGoogle Scholar
  10. 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 130:535–547CrossRefPubMedGoogle Scholar
  11. Lassmann H, Petsche U, Kitz K, Baran H, Sperk G, Seitelberger F, Hornykiewicz O (1984) The role of brain edema in epileptic brain damage induced by systemic kainic acid injection. Neuroscience 13:691–704CrossRefPubMedGoogle Scholar
  12. Loscher W (2002) Animal models of epilepsy for the development of antiepileptogenic and disease-modifying drugs. A comparison of the pharmacology of kindling and post-status epilepticus models of temporal lobe epilepsy. Epilepsy Res 50:105–123CrossRefPubMedGoogle Scholar
  13. Lothman EW, Bertram EH, Bekenstein JW, Perlin JB (1989) Self-sustaining limbic status epilepticus induced by ‘continuous’ hippocampal stimulation: electrographic and behavioral characteristics. Epilepsy Res 3:107–119CrossRefPubMedGoogle Scholar
  14. Lux HD, Heinemann U, Dietzel I (1986) Ionic changes and alterations in the size of the extracellular space during epileptic activity. Adv Neurol 44:619–639PubMedGoogle Scholar
  15. Martin BS, Kapur J (2008) A combination of ketamine and diazepam synergistically controls refractory status epilepticus induced by cholinergic stimulation. Epilepsia 49:248–255CrossRefPubMedGoogle Scholar
  16. Meierkord H, Holtkamp M (2007) Non-convulsive status epilepticus in adults: clinical forms and treatment. Lancet Neurol 6:329–339CrossRefPubMedGoogle Scholar
  17. Meldrum BS, Brierley JB (1973) Prolonged epileptic seizures in primates. Ischemic cell change and its relation to ictal physiological events. Arch Neurol 28:10–17PubMedGoogle Scholar
  18. Meldrum BS, Vigouroux RA, Brierley JB (1973) Systemic factors and epileptic brain damage. Prolonged seizures in paralyzed, artificially ventilated baboons. Arch Neurol 29:82–87PubMedGoogle Scholar
  19. Pfeiffer M, Draguhn A, Meierkord H, Heinemann U (1996) Effects of gamma-aminobutyric acid (GABA) agonists and GABA uptake inhibitors on pharmacosensitive and pharmacoresistant epileptiform activity in vitro. Br J Pharmacol 119:569–577PubMedGoogle Scholar
  20. Racine RJ (1972) Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol 32:281–294CrossRefPubMedGoogle Scholar
  21. Rice AC, DeLorenzo RJ (1999) N-methyl-d-aspartate receptor activation regulates refractoriness of status epilepticus to diazepam. Neuroscience 93:117–123CrossRefPubMedGoogle Scholar
  22. Sankar R, Shin DH, Liu H, Mazarati A, Pereirad, V, Wasterlain CG (1998) Patterns of status epilepticus-induced neuronal injury during development and long-term consequences. J Neurosci 18:8382–8393PubMedGoogle Scholar
  23. Schmitz D, Empson RM, Gloveli T, Heinemann U (1997) Serotonin blocks different patterns of low Mg2+-induced epileptiform activity in rat entorhinal cortex, but not hippocampus. Neuroscience 76:449–458CrossRefPubMedGoogle Scholar
  24. Sperk G, Wieser R, Widmann R, Singer EA (1986) Kainic acid induced seizures: changes in somatostatin, substance P and neurotensin. Neuroscience 17:1117–1126CrossRefPubMedGoogle Scholar
  25. Trousseau A (1868) Lectures on clinical medicine delivered at the Hotel Dieu, Paris, vol 1 (trans: Bazire PV). New Sydenham Society, LondonGoogle Scholar
  26. Turski WA, Cavalheiro EA, Schwarz M, Czuczwar SJ, Kleinrok Z, Turski L (1983) Limbic seizures produced by pilocarpine in rats: behavioural, electroencephalographic and neuropathological study. Behav Brain Res 9:315–335CrossRefPubMedGoogle Scholar
  27. Vezzani A, Granata T (2005) Brain inflammation in epilepsy: experimental and clinical evidence. Epilepsia 46:1724–1743CrossRefPubMedGoogle Scholar
  28. Vezzani A, Sperk G, Colmers WF (1999) Neuropeptide Y: emerging evidence for a functional role in seizure modulation. Trends Neurosci 22:25–30CrossRefPubMedGoogle Scholar
  29. Walker MC, Perry H, Scaravilli F, Patsalos PN, Shorvon SD, Jefferys JG (1999) Halothane as a neuroprotectant during constant stimulation of the perforant path. Epilepsia 40:359–364CrossRefPubMedGoogle Scholar
  30. Wasterlain C, Chen JW (2006) Definition and classification of status epilepticus. In: Wasterlain C, Treiman DM (eds) Status epilepticus. Mechanisms and management. The MIT Press, Cambridge MA, pp 11–16Google Scholar

Copyright information

© Springer-Verlag London Limited 2010

Authors and Affiliations

  • Uwe Heinemann
    • 1
  • Martin Holtkamp
    • 2
  1. 1.Institute of Neurophysiology, CharitéUniversitätsmedizin BerlinTucholskystr. 2Germany
  2. 2.Department of Neurology, CharitéUniversitätsmedizin BerlinSchumannstrasse 20/21Germany

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