Activités épileptiques produites in vitro par le tissu temporal humain

Translated title of the contribution: Epileptiform activities generated in vitro by human temporal lobe tissue

G. Huberfeld, S. Clemenceau, I. Cohen, J. Pallud, L. Wittner, V. Navarro, M. Baulac, R. Miles

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Drug-resistant partial epilepsies, including temporal lobe epilepsies with hippocampal sclerosis and cortical dysplasias, offer the opportunity to study human epileptic activity in vitro since the preferred therapy often consists of the surgical removal of the epileptogenic zone. Slices of this tissue retain functional neuronal networks and may generate epileptic activity. The properties of cells in this tissue do not seem to be significantly changed, but excitatory synaptic characteristics are enhanced and GABAergic inhibition is preserved. Typically, epileptic activity is not generated spontaneously by the neocortex, whether dysplastic or not, but can be induced by convulsants. The initiation of ictal discharges in neocortex depends on both GABAergic signaling and increased extracellular potassium. In contrast, a spontaneous interictal-like activity is generated by tissues from patients with temporal lobe epilepsies associated with hippocampal sclerosis. This activity is initiated not in the hippocampus but in the subiculum, an output region that projects to the entorhinal cortex. Interictal events seem to be triggered by GABAergic cells, which paradoxically excite approximately 20% of subicular pyramidal cells, while simultaneously inhibiting the majority. Interictal discharges are therefore sustained by both GABAergic and glutamatergic signaling. The atypical depolarizing effects of GABA depend on a pathological elevation in the basal levels of chloride in some subicular cells, similar to those of developmentally immature cells. This defect is caused by the perturbation of the expression of the cotransporters regulating the intracellular chloride concentration, the importer NKCC1, and the extruder KCC2. Blockade of excessive NKCC1 by the diuretic bumetanide restores intracellular chloride and thus hyperpolarizing GABAergic actions, suppressing interictal activity.

Original languageFrench
Pages (from-to)148-158
Number of pages11
JournalNeurochirurgie
Volume54
Issue number3
DOIs
Publication statusPublished - May 2008

Fingerprint

Temporal Lobe
Chlorides
Temporal Lobe Epilepsy
Neocortex
Sclerosis
Hippocampus
Bumetanide
Malformations of Cortical Development
Convulsants
Entorhinal Cortex
Partial Epilepsy
Pyramidal Cells
Diuretics
Human Activities
gamma-Aminobutyric Acid
Potassium
Stroke
In Vitro Techniques
Therapeutics

Keywords

  • Epilepsy
  • GABA receptors
  • Human
  • In vitro
  • Subiculum

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Huberfeld, G., Clemenceau, S., Cohen, I., Pallud, J., Wittner, L., Navarro, V., ... Miles, R. (2008). Activités épileptiques produites in vitro par le tissu temporal humain. Neurochirurgie, 54(3), 148-158. https://doi.org/10.1016/j.neuchi.2008.02.004

Activités épileptiques produites in vitro par le tissu temporal humain. / Huberfeld, G.; Clemenceau, S.; Cohen, I.; Pallud, J.; Wittner, L.; Navarro, V.; Baulac, M.; Miles, R.

In: Neurochirurgie, Vol. 54, No. 3, 05.2008, p. 148-158.

Research output: Contribution to journalArticle

Huberfeld, G, Clemenceau, S, Cohen, I, Pallud, J, Wittner, L, Navarro, V, Baulac, M & Miles, R 2008, 'Activités épileptiques produites in vitro par le tissu temporal humain', Neurochirurgie, vol. 54, no. 3, pp. 148-158. https://doi.org/10.1016/j.neuchi.2008.02.004
Huberfeld, G. ; Clemenceau, S. ; Cohen, I. ; Pallud, J. ; Wittner, L. ; Navarro, V. ; Baulac, M. ; Miles, R. / Activités épileptiques produites in vitro par le tissu temporal humain. In: Neurochirurgie. 2008 ; Vol. 54, No. 3. pp. 148-158.
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