title: Spreading depression triggers ictaform activity in partially disinhibited neuronal tissues.
abstract: There is unequivocal electrophysiological evidence that spreading depression (SD) can trigger epileptiform field potentials. In vitro experiments on human brain tissues indicated that γ-aminobutyric acid (GABA)-mediated inhibition prevented this process. Intra- and extracellular recordings of bioelectrical activities were performed in the rodent neocortex, hippocampus and amygdala after perfusion of low concentrations of the GABAA antagonist bicuculline and induction of SD by KCl application. Induction of SD in combined amygdala-hippocampus-cortex slices pre-treated with low concentration of bicuculline triggered epileptiform burst discharges in cortical as well as subcortical brain structures. Propagation of SD significantly depolarized the membrane, decreased the amplitude and duration of action potentials (APs) and after-hyperpolarization as well as the neuronal membrane input resistance and the amplitude of threshold potentials. Ten to twenty minutes after induction of SD, the pattern of APs changed from regular firing to a series of APs riding on an underlying paroxysmal depolarization shift before the appearance of typical ictaform activities. Changes of characteristic features of APs occurred after SD persisted during the appearance of epileptiform activities. These results indicate that SD increases neuronal excitability and facilitates synchronization of neuronal discharges in the presence of partial disinhibition of neuronal tissues. Our findings might explain the occurrence of seizures in neurological disorders with partial impairment of inhibitory tone, such as brain ischemia and epilepsy.
authors.affiliation: Institute of Physiology I, University of Münster, Münster, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Eickhoff
authors.affiliation: Department of Neurology, University of Münster, Münster, Germany; UCL Institute of Neurology, University College London, London, UK.
authors.forename: Stjepana
authors.initials: S
authors.lastname: Kovac
authors.affiliation: Shefa Neuroscience Research Center, Tehran, Iran.
authors.forename: Parviz
authors.initials: P
authors.lastname: Shahabi
authors.affiliation: Klinik und Poliklinik für Neurochirurgie, University of Münster, Münster, Germany.
authors.forename: Maryam Khaleghi
authors.initials: MK
authors.lastname: Ghadiri
authors.affiliation: Centre for Stroke Research Berlin, Charité University Medicine Berlin, Germany.
authors.forename: Jens P
authors.initials: JP
authors.lastname: Dreier
authors.affiliation: Klinik und Poliklinik für Neurochirurgie, University of Münster, Münster, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Stummer
authors.affiliation: Institute of Physiology I, University of Münster, Münster, Germany; Epilepsy Research Center, University of Münster, Münster, Germany.
authors.forename: Erwin-Josef
authors.initials: EJ
authors.lastname: Speckmann
authors.affiliation: Institute of Physiology I, University of Münster, Münster, Germany.
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Pape
authors.affiliation: Institute of Physiology I, University of Münster, Münster, Germany; Department of Neurology, University of Münster, Münster, Germany; Shefa Neuroscience Research Center, Tehran, Iran; Klinik und Poliklinik für Neurochirurgie, University of Münster, Münster, Germany; Epilepsy Research Center, University of Münster, Münster, Germany. Electronic address: gorjial@uni-muenster.de.
authors.forename: Ali
authors.initials: A
authors.lastname: Gorji
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001703:Biophysics; D001921:Brain / Q000166:cytology*; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D058787:GABA-A Receptor Antagonists; D001640:Bicuculline
keywords: Cerebrovascular disorders; Migraine aura; Refractory epilepsy; Seizure attacks; Spreading depression