The Functional and Structural Impact of Epileptic Seizures on the Developing Brain

  • Aristea S. GalanopoulouEmail author
  • Antonietta Coppola
  • Emmanuel Raffo
Reference work entry

Introduction and Definitions

Seizures are particularly common early in life and especially during the neonatal and infantile periods. Their clinical semiology, comorbidities, as well the type of epilepsies that evolve later differ from those that appear in adults. Of imminent clinical interest is to predict when brain dysfunction will occur after a first seizure, when epilepsy will develop, and what will be the best way to prevent or treat seizures and their comorbidities. Essential tools in the quest for such answers have been the in vivo and in vitro models of seizures and epilepsies. These model brief (lasting a few minutes) or longer (typically less than 30 min) isolated episodes of seizures, as well as status epilepticus (SE), i.e., continuous or frequent seizure activity for at least 30 min without interictal recovery ( Induced and Acquired Epileptogenicity in Animal Models). Studies on the effects of seizures at distinct developmental ages have well established that the...


Status Epilepticus Dentate Gyrus Mossy Fiber Febrile Seizure Hippocampal Sclerosis 
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


Dentate gyrus


Kainic acid


Magnetic resonance imaging




Status epilepticus



We would like to acknowledge the funding by NIH NINDS research grants NS20253, NS58303, NS45243, NINDS/NICHD grant NS62947 as well as grants from People Against Childhood Epilepsy, the International Rett Syndrome Foundation, Johnson & Johnson, and the Heffer Family Foundation. We are grateful to our technicians Ms Qianyun Li, Ms Wei Liu and Mrs Hong Wong for their outstanding technical assistance.


  1. Albala BJ, Moshe SL, Okada R (1984) Kainic-acid-induced seizures: a developmental study. Brain Res 315(1):139–148PubMedGoogle Scholar
  2. Avishai-Eliner S, Brunson KL, Sandman CA, Baram TZ (2002) Stressed-out, or in (utero)? Trends Neurosci 25(10):518–524CrossRefPubMedGoogle Scholar
  3. Berg AT (2008) Risk of recurrence after a first unprovoked seizure. Epilepsia 49(Suppl 1):13–18CrossRefPubMedGoogle Scholar
  4. Bo T, Jiang Y, Cao H, Wang J, Wu X (2004) Long-term effects of seizures in neonatal rats on spatial learning ability and N-methyl-D-aspartate receptor expression in the brain. Brain Res Dev Brain Res 152(2):137–142CrossRefPubMedGoogle Scholar
  5. Carson RC, Wilkinson M (1989) Seizure-induced delay of puberty in female rats: effects of age, stress and opioid antagonists. J Endocrinol 121(2):229–238CrossRefPubMedGoogle Scholar
  6. Cohen I, Navarro V, Clemenceau S, Baulac M, Miles R (2002) On the origin of interictal activity in human temporal lobe epilepsy in vitro. Science 298(5597):1418–1421CrossRefPubMedGoogle Scholar
  7. Cornejo BJ, Mesches MH, Benke TA (2008) A single early-life seizure impairs short-term memory but does not alter spatial learning, recognition memory, or anxiety. Epilepsy Behav 13(4):585–592CrossRefPubMedGoogle Scholar
  8. Druga R, Kubova H, Suchomelova L, Haugvicova R (2003) Lithium/pilocarpine status epilepticus-induced neuropathology of piriform cortex and adjoining structures in rats is age-dependent. Physiol Res 52(2):251–264PubMedGoogle Scholar
  9. Dube C, da Silva Fernandes MJ, Nehlig A (2001) Age-dependent consequences of seizures and the development of temporal lobe epilepsy in the rat. Dev Neurosci 23(3):219–223CrossRefPubMedGoogle Scholar
  10. Galanopoulou AS (2008a) Dissociated gender-specific effects of recurrent seizures on GABA signaling in CA1 pyramidal neurons: role of GABA(A) receptors. J Neurosci 28(7):1557–1567CrossRefPubMedGoogle Scholar
  11. Galanopoulou AS (2008b) GABA(A) receptors in normal development and seizures: friends or foes? Curr Neuropharmacol 6(1):1–20CrossRefPubMedGoogle Scholar
  12. Galanopoulou AS, Velisek L, Moshé SL (2009) Seizures and antiepileptic drugs in experimental animals: does exposure alter normal brain development? In: Janigro D (ed) Mammalian Brain Dev. Springer, pp 105–132Google Scholar
  13. Gilbert ME, Cain DP (1985) A single neonatal pentylenetetrazol or hyperthermia convulsion increases kindling susceptibility in the adult rat. Brain Res 354(2):169–180PubMedGoogle Scholar
  14. Giorgi FS, Malhotra S, Hasson H, Veliskova J, Rosenbaum DM, Moshe SL (2005) Effects of status epilepticus early in life on susceptibility to ischemic injury in adulthood. Epilepsia 46(4):490–498CrossRefPubMedGoogle Scholar
  15. Haas KZ, Sperber EF, Opanashuk LA, Stanton PK, Moshe SL (2001) Resistance of immature hippocampus to morphologic and physiologic alterations following status epilepticus or kindling. Hippocampus 11(6):615–625CrossRefPubMedGoogle Scholar
  16. Hauser WA (1994) The prevalence and incidence of convulsive disorders in children. Epilepsia 35(Suppl 2):S1–6CrossRefPubMedGoogle Scholar
  17. Holmes GL (2004) Effects of early seizures on later behavior and epileptogenicity. Ment Retard Dev Disabil Res Rev 10(2):101–105CrossRefPubMedGoogle Scholar
  18. Holmes GL, Sarkisian M, Ben-Ari Y, Chevassus-Au-Louis N (1999) Mossy fiber sprouting after recurrent seizures during early development in rats. J Comp Neurol 404(4):537–553CrossRefPubMedGoogle Scholar
  19. Holopainen IE (2008) Seizures in the developing brain: cellular and molecular mechanisms of neuronal damage, neurogenesis and cellular reorganization. Neurochem Int 52(6):935–947CrossRefPubMedGoogle Scholar
  20. Liu Z, Yang Y, Silveira DC, Sarkisian MR, Tandon P, Huang LT, Stafstrom CE, Holmes GL (1999) Consequences of recurrent seizures during early brain development. Neuroscience 92(4):1443–1454CrossRefPubMedGoogle Scholar
  21. Marcon J, Gagliardi B, Balosso S, Maroso M, Noe F, Morin M, Lerner-Natoli M, Vezzani A, Ravizza T (2009) Age-dependent vascular changes induced by status epilepticus in rat forebrain: implications for epileptogenesis. Neurobiol Dis 34(1):121–132CrossRefPubMedGoogle Scholar
  22. Moshe SL, Albala BJ (1982) Kindling in developing rats: persistence of seizures into adulthood. Brain Res 256(1):67–71PubMedGoogle Scholar
  23. Moshe SL, Albala BJ, Ackermann RF, Engel J Jr (1983) Increased seizure susceptibility of the immature brain. Brain Res 283(1):81–85PubMedGoogle Scholar
  24. Nairismagi J, Pitkanen A, Kettunen MI, Kauppinen RA, Kubova H (2006) Status epilepticus in 12-day-old rats leads to temporal lobe neurodegeneration and volume reduction: a histologic and MRI study. Epilepsia 47(3):479–488CrossRefPubMedGoogle Scholar
  25. Pekcec A, Fuest C, Muhlenhoff M, Gerardy-Schahn R, Potschka H (2008) Targeting epileptogenesis-associated induction of neurogenesis by enzymatic depolysialylation of NCAM counteracts spatial learning dysfunction but fails to impact epilepsy development. J Neurochem 105(2):389–400CrossRefPubMedGoogle Scholar
  26. Porter BE (2008) Neurogenesis and epilepsy in the developing brain. Epilepsia 49(Suppl 5):50–54CrossRefPubMedGoogle Scholar
  27. Rakhade SN, Jensen FE (2009) Epileptogenesis in the immature brain: emerging mechanisms. Nat Rev Neurol 5(7):380–391CrossRefPubMedGoogle Scholar
  28. Ravizza T, Rizzi M, Perego C, Richichi C, Veliskova J, Moshe SL, De Simoni MG, Vezzani A (2005) Inflammatory response and glia activation in developing rat hippocampus after status epilepticus. Epilepsia 46(Suppl 5):113–117CrossRefPubMedGoogle Scholar
  29. Roch C, Leroy C, Nehlig A, Namer IJ (2002) Predictive value of cortical injury for the development of temporal lobe epilepsy in 21-day-old rats: an MRI approach using the lithium-pilocarpine model. Epilepsia 43(10):1129–1136CrossRefPubMedGoogle Scholar
  30. Sanabria Ydel C, Arganaraz GA, Lima E, Priel MR, Trindade Eda S, Loeb LM, Scorza FA, Cavalheiro EA, Amado D, Naffah-Mazzacoratti Mda G (2008) Neurogenesis induced by seizures in the dentate gyrus is not related to mossy fiber sprouting but is age dependent in developing rats. Arq Neuropsiquiatr 66(4):853–860PubMedGoogle Scholar
  31. Sankar R, Shin DH, Liu H, Mazarati A, Pereira de Vasconcelos A, Wasterlain CG (1998) Patterns of status epilepticus-induced neuronal injury during development and long-term consequences. J Neurosci 18(20):8382–8393PubMedGoogle Scholar
  32. Sillanpaa M, Shinnar S (2002) Status epilepticus in a population-based cohort with childhood-onset epilepsy in Finland. Ann Neurol 52(3):303–310CrossRefPubMedGoogle Scholar
  33. Stafstrom CE, Thompson JL, Holmes GL (1992) Kainic acid seizures in the developing brain: status epilepticus and spontaneous recurrent seizures. Brain Res Dev Brain Res 65(2):227–236CrossRefPubMedGoogle Scholar
  34. Sutula TP, Hagen J, Pitkanen A (2003) Do epileptic seizures damage the brain? Curr Opin Neurol 16(2):189–195CrossRefPubMedGoogle Scholar
  35. Swann JW, Le JT, Lee CL (2007) Recurrent seizures and the molecular maturation of hippocampal and neocortical glutamatergic synapses. Dev Neurosci 29(1–2):168–178CrossRefPubMedGoogle Scholar
  36. Wasterlain CG, Niquet J, Thompson KW, Baldwin R, Liu H, Sankar R, Mazarati AM, Naylor D, Katsumori H, Suchomelova L, Shirasaka Y (2002) Seizure-induced neuronal death in the immature brain. Prog Brain Res 135:335–353CrossRefPubMedGoogle Scholar
  37. 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(2):403–418CrossRefPubMedGoogle Scholar
  38. Zhang G, Raol YH, Hsu FC, Coulter DA, Brooks-Kayal AR (2004) Effects of status epilepticus on hippocampal GABAA receptors are age-dependent. Neuroscience 125(2):299–303CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag London Limited 2010

Authors and Affiliations

  • Aristea S. Galanopoulou
    • 2
    Email author
  • Antonietta Coppola
    • 1
  • Emmanuel Raffo
    • 1
  1. 1.Department of NeurologyAlbert Einstein College of Medicine, Yeshiva University10461, BronxUSA
  2. 2.Department of NeurologyAlbert Einstein College of Medicine of Yeshiva University10461, BronxUSA

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