title: Cell swelling precedes seizures induced by inhibition of astrocytic metabolism.
abstract: It is currently unknown what processes take place at the interface between non-ictal and ictal activity during seizure initiation. In this study, using paralysed awake rats, we focally inhibited astrocytic metabolism with fluorocitrate (FC), causing seizures. We measured changes in electroencephalogram (EEG) (0-300 Hz), and extracellular ion-concentrations during ictal onsets defining possible relationships with impedance-determined cell swelling. In animals showing ictal activity (69%) there were spike-wave discharges, spike-wave discharges followed by spreading depression and spreading depression without any discharges. In a high proportion of spike-wave discharges (>95%), just prior to the first spike-wave discharge, there was a decrease in the volume of the extracellular space. Following the initiation of cell swelling and prior to discharges, there were increases in high-frequency (150-300 Hz) EEG activity, increases in extracellular potassium- and decreases in extracellular calcium-concentrations. We suggest that EEG and ionic changes are not causative of cell swelling. Cell swelling due to metabolic failure in astrocytes at the injected site may release excitatory amino acids. At the same time, our results suggest ion homeostasis is not maintained and increased neuronal excitability and synchronisation occur. These could be the drivers changing normal brain activity into ictal activity.
authors.affiliation: Center for Neuroscience and Department of Medicine, Flinders University, Adelaide 5001, South Australia, Australia. marita.broberg@flinders.edu
authors.forename: Marita
authors.initials: M
authors.lastname: Broberg
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Pope
authors.forename: Trent
authors.initials: T
authors.lastname: Lewis
authors.forename: Torsten
authors.initials: T
authors.lastname: Olsson
authors.forename: Michael
authors.initials: M
authors.lastname: Nilsson
authors.forename: John O
authors.initials: JO
authors.lastname: Willoughby
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000209:etiology*; D002118:Calcium / Q000378:metabolism; D002951:Citrates; D013181:Cortical Spreading Depression / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D017097:Electric Impedance; D004569:Electroencephalography / Q000187:drug effects / Q000379:methods; D045604:Extracellular Fluid / Q000378:metabolism*; D008297:Male; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology; D013997:Time Factors; D014882:Water-Electrolyte Balance / Q000502:physiology*
chemical_list: D002951:Citrates; C007744:fluorocitrate; D011188:Potassium; D002118:Calcium