FNWI building SILS-CNS part 1
FNWI building SILS-CNS part 2

SILS Swammerdam Institute for Life Sciences - CNS





EPILEPSY   RESEARCH



Amsterdam Science Park


Mesial temporal lobe epilepsy is a disorder that is characterized by complex partial seizures and hippocampal sclerosis. There is a strong suggestion of progression of symptoms in patients with this disorder. With time, seizures become more disabling and interictal behavioral disturbances can appear. Moreover, a large percentage of these patients are refractory to treatment, in other words pharmacoresistant.


Early intervention, (presently still by anterior temporal lobe resection) can improve the chances of a seizure free future. It is of crucial importance to perform animal research on all aspects of the progressive nature of epilepsy in order to develop hypotheses that will direct productive clinical investigations. In our group we use animal models (rat and mouse) for mesial temporal lobe epilepsy. The models are characterized by having spontaneous seizures after a latent period that follows the initial electrically or pharmacologically evoked status epilepticus (SE). We are interested in the mechanisms that lead to the occurrence of spontaneous seizures (epilepsy). We use anatomical (tracing, immunostaining, histochemistry), molecular (in situ hybridization, PCR, western blot, microarrays) and neurophysiological (EEG, laminar field potentials in vivo and in vitro brain slices) and neurochemical (HPLC) techniques at different time points after SE in order to get insight in the processes that lead to epilepsy. We focus mainly on 2 questions :



  • What are the underlying mechanisms by which epilepsy develops.
  • Which mechanisms contribute to pharmacoresistance.

Findings that we obtain in our animal models will be also studied in brain material of epileptic patients (obtained from surgery, collaboration Neuropathology, AMC). Insights into the mechanisms of epileptogenesis and pharmacoresistance may ultimately lead to new therapies that will allow more effective treatments and possibly even a way of preventing epilepsy.

Media and news


Nationaal Epilepsie Fonds grant received april 2010
Jan Gorter (SILS, UvA), received a grant for his research project
"Immune suppression as anti-epileptogenic strategy in animal models
of temporal lobe epilepsy" 		UvA nieuws (Dutch)
Harry Meinardi Prize 2010 UvA nieuws (Dutch)
Thesis Erwin van Vliet home page Erwin van Vliet

click for larger image

Figure 1 immuno-double labeling, showing the neuronal marker NeuN (green)
and the neuronal glutamate transporter, EAAC1 (red)
Note the strong decrease of EAAC1 expression in the inner molecular layer
(iml; where mossy fibers sprout to) in epileptic rat (B) compared to control rat (A).
click for larger image

click for larger image

Figure 2 anatomical tracing of presubicular projections with BDA (red)
to entorhinal cortex layer II / III neurons (green)
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Figure 3 microarray analysis revealed prominent activation
of the complement cascade in the latent period
click for larger image




Colloborations (past and present), national


Colloborations, international



People in the group (July 2010)

Contact :

J.A. Gorter, PhD
Center for Neuroscience, Swammerdam Institute for Life Sciences
University of Amsterdam
Science Park 904
1098 XH Amsterdam
The Netherlands

Phone: +31-20-5257893
Fax: +31-20-5257709
e-mail :



Publications

  • E.A. van Vliet, G. Zibell, A. Pekcec, J. Schlichtiger, P.M. Edelbroek,
    L. Holtman, E. Aronica, J.A.Gorter, H. Potschka. (2010)
    COX-2 inhibition controls P-glycoprotein expression and promotes brain
    delivery of the anti-epileptic drug phenytoin in chronic epileptic rats.
    Neuropharmacology 2010, 58(2):404-12.

  • E. Aronica, K. Fluiter, A. Iyer, E. Zurolo, J. Vreijling, E.A. van Vliet, J.C. Baayen,J.A. Gorter (2010)
    Expression pattern of miR-146a, an inflammation-associated microRNA,
    in experimental and human temporal lobe epilepsy.
    Eur J Neurosci 2010, 31(6):1098-9

  • E.A. van Vliet, P.M. Edelbroek, J.A. Gorter. (2010)
    Improved seizure control by alternating therapy of levetiracetam and valproate in epileptic rats
    Epilepsia 2010, 51(3):362-70.

  • A. Pekcec, B. Unkruer, J. Schlichtiger, J. Soerensen, A.M.S. Hartz,
    B. Bauer, E.A. van Vliet, J.A. Gorter, H. Potschka (2009)
    Targeting prostaglandin E2 EP1 receptors prevents seizure-associated p- glycoprotein up-regulation.
    JPET 2009; 330:939-947.

  • Farmacoresistente epilepsie: mogelijke oorzaken. in Epilepsie, periodiek voor professionals 2009, 3(7):27-29.

  • E.A. van Vliet, E. Aronica, S. Redeker, K. Boer, J.A.Gorter (2009)
    Decreased expression of synaptic vesicle protein 2A, the binding site for levetiracetam, during epileptogenesis and chronic epilepsy.
    Epilepsia 2009;50(3):422-33.

  • L. Holtman, E.A. van Vliet, R. van Schaik, C.M. Queiroz, E. Aronica, J.A. Gorter (2009)
    Effects of SC58236, a selective COX-2 inhibitor, on epileptogenesis and spontaneous seizures in a rat model for temporal lobe epilepsy. Ep Res 2009;84:56- 66.

  • E.A. van Vliet,R. van Schaik, P.M. Edelbroek, F.H. Lopes da Silva, W.J. Wadman, J.A. Gorter (2008)
    Development of tolerance to levetiracetam in rats with chronic epilepsy.
    Epilepsia 2008;49(7):1151-9.

  • Therapieresistentie: te strenge controle bij Checkpoint Charley? E.A. van Vliet (2007)
    Episcoop 2007; 3: 22-24.

  • van Vliet EA, da Costa Araujo S, Redeker S, van Schaik R, Aronica E and Gorter JA (2007).
    Blood-brain barrier leakage may lead to progression of temporal lobe epilepsy. Brain 130(Pt 2): 521-34.

  • Gorter JA, Van Vliet EA, Rauwerda H, Breit T, Stad R, van Schaik L, Vreugdenhil E, Redeker S, Hendriksen E, Aronica E, Lopes da Silva FH and Wadman WJ (2007)
    Dynamic Changes of Proteases and Protease Inhibitors Revealed by Microarray Analysis in CA3 and Entorhinal Cortex during Epileptogenesis in the Rat. Epilepsia 48(s5): 53-64.

  • Aronica E, Boer K, van Vliet EA, Redeker S, Baayen JC, Spliet WG, van Rijen PC, Troost D, Lopes da Silva FH, Wadman WJ and Gorter JA (2007)
    Complement activation in experimental and human temporal lobe epilepsy. Neurobiol Dis 26(3): 497-511.

  • Aronica E, Boer K, Redeker S, Spliet WG, van Rijen PC, Troost D and Gorter JA (2007)
    Differential expression patterns of chloride transporters, Na+-K+-2Cl--cotransporter and K+-Cl--cotransporter, in epilepsy-associated malformations of cortical development. Neuroscience 145(1): 185-96.

  • van Vliet EA, van Schaik R, Edelbroek PM, Redeker S, Aronica E, Wadman WJ, Marchi N, Vezzani A and Gorter JA (2006).
    Inhibition of the multidrug transporter P-glycoprotein improves seizure control in phenytoin-treated chronic epileptic rats. Epilepsia 47(4): 672-80.

  • Gorter JA, van Vliet EA, Aronica E, Breit T, Rauwerda H, Lopes da Silva FH and Wadman WJ (2006).
    Potential new antiepileptogenic targets indicated by microarray analysis in a rat model for temporal lobe epilepsy. J Neurosci 26(43): 11083-110.

  • Tolner EA, Kloosterman F, van Vliet EA, Witter MP, Silva FH and Gorter JA (2005).
    Presubiculum stimulation in vivo evokes distinct oscillations in superficial and deep entorhinal cortex layers in chronic epileptic rats. J Neurosci 25(38): 8755-65.

  • van Vliet EA, Aronica E, Tolner EA, Lopes da Silva FH and Gorter JA (2004).
    Progression of temporal lobe epilepsy in the rat is associated with immunocytochemical changes in inhibitory interneurons in specific regions of the hippocampal formation. Exp Neurol 187(2): 367-79.

  • Holtmaat AJ, Gorter JA, Wit JD, Tolner EA, Spijker S, Giger RJ, Lopes da Silva FH and Verhaagen J (2003).
    Transient downregulation of sema3a mRNA in a rat model for temporal lobe epilepsy. A novel molecular event potentially contributing to mossy fiber sprouting. Exp Neurol 182(1): 142-50.

  • Gorter JA, Goncalves Pereira PM, van Vliet EA, Aronica E, Lopes da Silva FH and Lucassen PJ (2003).
    Neuronal cell death in a rat model for mesial temporal lobe epilepsy is induced by the initial status epilepticus and not by later repeated spontaneous seizures. Epilepsia 44(5): 647-58.

  • Rizzi M, Caccia S, Guiso G, Richichi C, Gorter JA, Aronica E, Aliprandi M, Bagnati R, Fanelli R, D'Incalci M, Samanin R and Vezzani A (2002).
    Limbic seizures induce P-glycoprotein in rodent brain: functional implications for pharmacoresistance. J Neurosci 22(14): 5833-9.

  • Gorter JA, Van Vliet EA, Proper EA, De Graan PN, Ghijsen WE, Lopes Da Silva FH and Aronica E (2002).
    Glutamate transporters alterations in the reorganizing dentate gyrus are associated with progressive seizure activity in chronic epileptic rats. J Comp Neurol 442(4): 365-77.

  • Gorter JA, Van Vliet EA, Aronica E and Lopes da Silva FH (2001).
    Progression of spontaneous seizures after status epilepticus is associated with mossy fibre sprouting and extensive bilateral loss of hilar parvalbumin and somatostatin-immunoreactive neurons. Eur J Neurosci 13(4): 657-669.

  • Aronica E, Vliet van EA, Mayboroda O, Troost D, Lopes da Silva FH and Gorter JA (2000).
    Upregulation of metabotropic glutamate receptor subtype mGluR3 and mGluR5 in reactive astrocytes in a rat model of mesial temporal lobe epilepsy. Eur J Neurosci 12(7): 2333-2345.


This page was last updated on 6 june 2010

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