Article
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
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Published: | May 4, 2005 |
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Outline
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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)