gms | German Medical Science

56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
3èmes journées françaises de Neurochirurgie (SFNC)

Deutsche Gesellschaft für Neurochirurgie e. V.
Société Française de Neurochirurgie

07. bis 11.05.2005, Strasbourg

In vitro triggering of epileptiform activity in the human hippocampal slices from patients operated on for pharmakoresistant temporal lobe epilepsy

In-vitro induzierte epileptiforme Aktivität in humanem Hippocampusgewebe von chirurgischen Patienten mit Temporallappen-Epilepsie

Meeting Abstract

  • corresponding author T.-N. Lehmann - Klinik für Neurochirurgie der Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin
  • S. Gabriel - Johannes-Müller-Institut für Physiologie, Berlin, Charité-Universitätsmedizin Berlin
  • M. Merschhemke - Epilepsie-Zentrum Berlin-Brandenburg, Evangelisches Krankenhaus Königin Elisabeth Herzberge, Berlin
  • H. J. Meencke - Epilepsie-Zentrum Berlin-Brandenburg, Evangelisches Krankenhaus Königin Elisabeth Herzberge, Berlin
  • U. Heinemann - Johannes-Müller-Institut für Physiologie, Berlin, Charité-Universitätsmedizin Berlin

Deutsche Gesellschaft für Neurochirurgie. Société Française de Neurochirurgie. 56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3èmes journées françaises de Neurochirurgie (SFNC). Strasbourg, 07.-11.05.2005. Düsseldorf, Köln: German Medical Science; 2005. Doc11.05.-12.01

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2005/05dgnc0233.shtml

Veröffentlicht: 4. Mai 2005

© 2005 Lehmann et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective

Selective neuronal cell loss in chronic epileptic hippocampus leads to reorganisation of the fibre system in the mesial temporal lobe. Particularly mossy fibres can sprout and form aberrant connections between granule cells of the dentate gyrus (DG). We studied the functional consequences of morphological alterations in hippocampal specimens.

Methods

Human resected hippocampi (n=32) from patients operated on for temporomesial epilepsy and/or tumour could be kept viably after slicing and transfer into interface recording chambers. Fluorescent dextran amine labeling and Timm’s stain were used to indicate aberrant neuronal connectivity of the granule cells in the DG. The presence of a hippocampal sclerosis was determined using the Wyler score. Low frequency antidrome stimulation of the granule cells in presence of elevated extracellular potassium concentration (10 and 12 mM) was applied to study the differences in induced in-vitro electrical activity according to the presence of aberrant connectivity within the DG.

Results

Aberrant Timm’s staining (88% of the slices) and retrogradely labelled mossy fibres (96%) together with granule cell dispersion (100%) within the DG indicated the network reorganisation in sclerotic hippocampi (Wyler Grade 3 and 4) whereas network alterations were rarely present in non-sclerotic hippocampi (5,6%, 9,5%, 0%, respectively). Abnormal electrical activity could be evoked in slices with and without neuronal reorganisation (27/40 slices, 14/20 patients and 11/22 slices, 6/12 patients, respectively). However, recurrent short discharges (mimicking periodic ictal spiking) and seizure-like events exclusively occurred in slices with network reorganisation (65%, 13/20) and never in those without altered connectivity. Statistically, the occurrence of such epileptiform activity with the presence of network reorganisation was significant (Chi2; p=0.002; C=0.589). The abnormal electrical activity could be blocked by low Ca++ and glutamate receptor antagonist pointing to its synaptic nature.

Conclusions

Our results show the coincidence of structural abnormality and epileptiform activity in sclerotic hippocampi suggesting that reorganisation might support the development of seizure activity in the hippocampus. Our model can be used to study mechanisms of pharmakoresistence and to test new antiepileptic drugs. By bridging the gap to basic neuroscience neurosurgery may strongly support further research in epileptogenesis.

(Supported by DFG SFB-TR 3)