title: Altered inhibition in the hippocampal neural networks after spreading depression.
abstract: Prolonged neuronal depression after spreading depression (SD) is followed by a late cellular and synaptic hyperexcitability. Intra- and extracellular recordings of bioelectrical activities were performed in the rodent hippocampus to investigate the role of γ-aminobutyric acid (GABA)-mediated inhibition in the late hyperexcitable state of SD. The effect of KCl-induced negative DC potential shifts was investigated on extracellularly recorded paired-pulse depression (PPD) and bicuculline-induced afterdischarges as well as intracellularly recorded inhibitory post synaptic potentials (IPSPs) in the hippocampal CA1 area. The results revealed that SD decreased the degree of PPD, enhanced the number and duration of bicuculline-induced afterdischarges, and reduced the amplitude and duration of IPSPs. Application of low concentrations of bicuculline before the induction of SD enhanced the inhibitory effect of SD on IPSPs. Data indicate the contribution of GABA-mediated inhibition to SD-induced delayed hyperexcitability. Modulation of GABA function in the late hyperexcitability phase of SD may play a role in therapeutic management of SD-related neurological disorders.
authors.affiliation: Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Mesgari
authors.affiliation: Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Ghaffarian
authors.affiliation: Department of Neurosurgery, Westfälische Wilhelms-Universität Münster, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Khaleghi Ghadiri
authors.affiliation: Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, USA.
authors.forename: H
authors.initials: H
authors.lastname: Sadeghian
authors.affiliation: Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, Germany.
authors.forename: E-J
authors.initials: EJ
authors.lastname: Speckmann
authors.affiliation: Department of Neurosurgery, Westfälische Wilhelms-Universität Münster, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Stummer
authors.affiliation: Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, Germany; Department of Neurology and Institute of Neurophysiology, Westfälische Wilhelms-Universität Münster, Germany; Shefa Neuroscience Research Center, Khatam-Alanbia Hospital, Tehran, Iran; Razavi Neuroscience Center, Razavi Hospital, Mashhad, Iran. Electronic address: gorjial@uni-muenster.de.
authors.forename: A
authors.initials: A
authors.lastname: Gorji
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology*; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology*; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D008839:Microelectrodes; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011189:Potassium Chloride; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D058787:GABA-A Receptor Antagonists; D005680:gamma-Aminobutyric Acid; D011189:Potassium Chloride; D001640:Bicuculline
keywords: disinhibition; epilepsy; hippocampus; migraine; spreading depolarization; stroke