A role for astroglia in epileptogenesis has been hypothesised but is not established. Low doses of
fluorocitrate specifically and reversibly disrupt astroglial metabolism by blocking
aconitase, an
enzyme integral to the tricarboxylic acid cycle. We used cerebral cortex
injections of
fluorocitrate, at a dose that we demonstrated to inhibit astroglial metabolism selectively, to determine whether astroglial disturbances lead to
seizures. Rats were
halothane-anesthetized, and 0.8 nmol of
sodium fluorocitrate was injected into the cerebral cortex. Extradural electroencephalogram (EEG)
electrodes were implanted, after which the
anesthesia was ceased and the animals were observed. In all experiments, 14 of 15
fluorocitrate-treated animals exhibited epileptiform EEG discharges, with some animals exhibiting convulsive
seizures. Discharges commenced as early as 30 min postfluorocitrate injection. Intraperitoneal octanol, but not
halothane by inhalation, given to test the possible participation of gap junctions in EEG discharge generation, blocked or delayed the occurrence of discharges after
fluorocitrate. These results indicate that focal cerebrocortical astroglial dysfunction leads to focal epileptiform discharges and sometimes to convulsive
seizures and that the process possibly depends on effects mediated by gap junctions.