Spreading depression triggers ictaform activity in partially disinhibited neuronal tissues

• Published in: Experimental neurology 2014-03, Vol.253, p.1-15
• Main Authors: Eickhoff, Marius, Kovac, Stjepana, Shahabi, Parviz, Khaleghi Ghadiri, Maryam, Dreier, Jens P., Stummer, Walter, Speckmann, Erwin-Josef, Pape, Hans-Christian, Gorji, Ali
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Animals; Bicuculline - pharmacology; Biological and medical sciences; Biophysics; Brain - cytology; Cerebrovascular disorders; Cortical Spreading Depression - drug effects; Cortical Spreading Depression - physiology; Electric Stimulation; GABA-A Receptor Antagonists - pharmacology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; In Vitro Techniques; Medical sciences; Migraine aura; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Nervous system (semeiology, syndromes); Neural Inhibition - drug effects; Neural Inhibition - physiology; Neurology; Neurons - drug effects; Neurons - physiology; Patch-Clamp Techniques; Rats; Rats, Wistar; Refractory epilepsy; Seizure attacks; Spreading depression; Time Factors; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2013.12.008

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. •Co-occurrence of spreading depolarization (SD) and epileptic activity was reported.•SD can trigger ictaform discharges (ID) in partially disinhibited neuronal tissues.•Partial disinhibition was reported in stroke and chronic epilepsy.•SD triggered ID may contribute to epileptogenesis in ischemia and epilepsy.