Free radical-mediated cell damage after experimental status epilepticus in hippocampal slice cultures

Richard Kovács, Sebastian Schuchmann, Siegrun Gabriel, Oliver Kann, J. Kardos, Uwe Heinemann

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Generation of free radicals may have a key role in the nerve cell damage induced by prolonged or frequently recurring convulsions (status epilepticus). Mitochondrial function may also be altered due to production of free radicals during seizures. We therefore studied changes in field potentials (fp) together with measurements of extracellular, intracellular, and intramitochondrial calcium concentration ([Ca2+]e, [Ca2+]i, and [Ca2+]m, respectively), mitochondrial membrane potential (ΔΨ), NAD(P)H auto-fluorescence, and dihydroethidium (HEt) fluorescence in hippocampal slice cultures by means of simultaneous electrophysiological and microfluorimetric measurements. As reported previously, each seizure-like event (SLE) resulted in mitochondrial depolarization associated with a delayed rise in oxidation of HEt to ethidum, presumably indicating ROS production. We show here that repeated SLEs led to a decline in intracellular and intramitochondrial Ca2+ signals despite unaltered Ca2+ influx. Also, mitochondrial depolarization and the NAD(P)H signal became smaller during recurring SLEs. By contrast, the ethidium fluorescence rises remained constant or even increased from SLE to SLE. After about 15 SLEs, activity changed to continuous afterdischarges with steady depolarization of mitochondrial membranes. Staining with a cell death marker, propidium iodide, indicated widespread cell damage after 2 h of recurring SLEs. The free radical scavenger, α-tocopherol, protected the slice cultures against this damage and also reduced the ongoing impairment of NAD(P)H production. These findings suggest involvement of reactive oxygen species (ROS) of mitochondrial origin in the epileptic cell damage and that free radical scavenging may prevent status epilepticus-induced cell loss.

Original languageEnglish
Pages (from-to)2909-2918
Number of pages10
JournalJournal of Neurophysiology
Volume88
Issue number6
Publication statusPublished - Dec 1 2002

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Status Epilepticus
Free Radicals
Seizures
NAD
Fluorescence
Reactive Oxygen Species
Free Radical Scavengers
Tocopherols
Ethidium
Propidium
Mitochondrial Membrane Potential
Mitochondrial Membranes
Cell Death
Staining and Labeling
Calcium
Neurons

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

Kovács, R., Schuchmann, S., Gabriel, S., Kann, O., Kardos, J., & Heinemann, U. (2002). Free radical-mediated cell damage after experimental status epilepticus in hippocampal slice cultures. Journal of Neurophysiology, 88(6), 2909-2918.

Free radical-mediated cell damage after experimental status epilepticus in hippocampal slice cultures. / Kovács, Richard; Schuchmann, Sebastian; Gabriel, Siegrun; Kann, Oliver; Kardos, J.; Heinemann, Uwe.

In: Journal of Neurophysiology, Vol. 88, No. 6, 01.12.2002, p. 2909-2918.

Research output: Contribution to journalArticle

Kovács, R, Schuchmann, S, Gabriel, S, Kann, O, Kardos, J & Heinemann, U 2002, 'Free radical-mediated cell damage after experimental status epilepticus in hippocampal slice cultures', Journal of Neurophysiology, vol. 88, no. 6, pp. 2909-2918.
Kovács, Richard ; Schuchmann, Sebastian ; Gabriel, Siegrun ; Kann, Oliver ; Kardos, J. ; Heinemann, Uwe. / Free radical-mediated cell damage after experimental status epilepticus in hippocampal slice cultures. In: Journal of Neurophysiology. 2002 ; Vol. 88, No. 6. pp. 2909-2918.
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